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The Antarctic polar vortex creates unique chemical and dynamical conditions when the stratospheric air over Antarctica is isolated from the rest of the stratosphere. As a result, stratospheric ozone within the vortex remains largely unchanged for a five-month period from April until late August when the sunrise and extremely cold temperatures create favorable conditions for rapid ozone loss. Such prolonged stable conditions within the vortex make it possible to estimate the total ozone levels there from sparse wintertime ozone observations at the South Pole. The available records of focused Moon (FM) observations by Dobson and Brewer spectrophotometers at the Amundsen-Scott South Pole Station (for the periods 1964–2022 and 2008–2022, respectively) as well as integrated ozonesonde profiles (1986–2022) and MERRA-2 reanalysis data (1980–2022) were used to estimate the total ozone variability and long-term changes over the South Pole. Comparisons with MERRA-2 reanalysis data for the period 1980–2022 demonstrated that the uncertainties of Dobson and Brewer daily mean FM values are about 2.5 %–4 %. Wintertime (April–August) MERRA-2 data have a bias with Dobson data of -8.5 % in 1980–2004 and 1.5 % in 2005–2022. The mean difference between wintertime Dobson and Brewer data in 2008–2022 was about 1.6 %; however, this difference can be largely explained by various systematic errors in Brewer data. The wintertime ozone values over the South Pole during the last 20 years were about 12 % below the pre-1980s level, i.e., the decline there was nearly twice larger than that over southern midlatitudes. It is probably the largest long-term ozone decline aside from the springtime Antarctic ozone depletion. While wintertime ozone decline over the pole has hardly any impact on the environment, it can be used as an indicator to diagnose the state of the ozone layer, particularly because it requires data from only one station. Dobson and ozonesonde data after 2001 show a small positive, but not statistically significant, trend in ozone values of about 1.5% per decade that is in line with the trend expected from the concentration of the ozone depleting substances in the stratosphere.

Balloon-borne ozonesondes launched weekly from South Pole Station (1986–2021) measure high-vertical-resolution profiles of ozone and temperature from the surface to 30–35 km altitude. The launch frequency is increased in late winter before the onset of rapid stratospheric ozone loss in September. Ozone hole metrics show that the yearly total column ozone and 14–21 km partial column ozone minimum values and September loss rate trends have been improving (less severe) since 2001. The 36-year record also shows interannual variability, especially in recent years (2019–2021). Here we show additional details of these 3 years by comparing annual minimum profiles observed on the date when the lowest integrated total column ozone occurs. We also compare the July–December time series of the 14–21 km partial column ozone values to the 36-year median with percentile intervals. The 2019 anomalous vortex breakdown showed stratospheric temperatures began warming in early September followed by reduced ozone loss. The minimum total column ozone of 180 Dobson units (DU) was observed on 24 September. This was followed by two stable and cold polar vortex years during 2020 and 2021 with total column ozone minimums at 104 DU (1 October) and 102 DU (7 October), respectively. These years also showed broad near-zero-ozone (loss saturation) regions within the 14–21 km layer by the end of September which persisted into October. Validation of the ozonesonde observations is conducted through the ongoing comparison of total column ozone measurements with the South Pole ground-based Dobson spectrophotometer. The ozonesondes show a more positive bias of 2 ± 3 % (higher) than the Dobson following a thorough evaluation and homogenization of the long-term ozonesonde record completed in 2018.

The United States government has operated Dobson ozone spectrophotometers at various sites, starting during the International Geophysical Year (1 July 1957 to 31 December 1958). A network of stations for long-term monitoring of the total column content (thickness of the ozone layer) of the atmosphere was established in the early 1960s and eventually grew to 16 stations, 14 of which are still operational and submit data to the United States of America's National Oceanic and Atmospheric Administration (NOAA). Seven of these sites are also part of the Network for the Detection of Atmospheric Composition Change (NDACC), an organization that maintains its own data archive. Due to recent changes in data processing software the entire dataset was re-evaluated for possible changes. To evaluate and minimize potential changes caused by the new processing software, the reprocessed data record was compared to the original data record archived in the World Ozone and UV Data Center (WOUDC) in Toronto, Canada. The history of the observations at the individual stations, the instruments used for the NOAA network monitoring at the station, the method for reducing zenith-sky observations to total ozone, and calibration procedures were re-evaluated using data quality control tools built into the new software. At the completion of the evaluation, the new datasets are to be published as an update to the WOUDC and NDACC archives, and the entire dataset is to be made available to the scientific community. The procedure for reprocessing Dobson data and the results of the reanalysis on the archived record are presented in this paper. A summary of historical changes to 14 station records is also provided.

Three reference Dobsons (regional standard Dobsons No. 064, Germany and No. 074, Czech Republic as well as the world standard No. 083, USA) were optically characterized at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig in 2015 and at the Czech Metrology Institute (CMI) in Prague in 2016 within the EMRP ENV 059 project “Traceability for atmospheric total column ozone”. Slit functions and the related parameters of the instruments were measured and compared with G. M. B. Dobson's specifications in his handbook. All Dobsons show a predominantly good match of the slit functions and the peak (centroid) wavelengths with deviations between −0.11 and +0.12 nm and differences of the full width half maximum (FWHM) between 0.13 and 0.37 nm compared to the nominal values at the shorter wavelengths. Slightly larger deviations of the FWHMs from the nominal Dobson data, up to 1.22 nm, can be seen at the longer wavelengths, especially for the slit function of the long D-wavelength. However, differences between the effective absorption coefficients (EACs) for ozone derived using Dobson's nominal values of the optical parameters on one hand and these measured values on the other hand are not too large in the case of both “old” Bass–Paur (BP) and “new” IUP-ozone (Institut für Umweltphysik, University of Bremen) absorption cross sections. Their inclusion in the calculation of the total ozone column (TOC) leads to improvements of significantly less than ±1 % at the AD-wavelengths between −1 and −2 % at the CD-wavelengths pairs in the BP-scale. The effect on the TOC in the IUP-scale is somewhat larger at the AD-wavelengths, up to +1 % (D074), and smaller at the CD-wavelengths pair, from −0.44 to −1.5 %. Beside this positive effect gained from the data with higher metrological quality that is needed for trend analyses and satellite validation, it will be also possible to explain uncommon behaviours of field Dobsons during calibration services, especially when a newly developed transportable device TuPS (tuneable portable radiation source) from CMI proves its capability to provide similar results as the stationary setups in the laboratories of National Metrology Institutes. Then, the field Dobsons can be optically characterized as well during regular calibration campaigns. A corresponding publication will be prepared using the results of TuPS-based measurements of more than 10 Dobsons in field campaigns in 2017.

The United States government has operated Dobson Ozone Spectrophotometers at various sites, starting during the International Geophysical Year (July 1, 1957 to December 31, 1958). A network of stations for longterm monitoring of the total column content (thickness of the ozone layer) of the atmosphere was established in the early 1960s, and eventually grew to sixteen stations, fourteen of which are still operational and submit data to the United States of America’s National Oceanic and Atmospheric Administration (NOAA). Seven of these sites are also part of the Network for the Detection of Atmospheric Composition Change (NDACC), an organization that maintains its own data archive. Due to recent changes in data processing software the entire data set was reevaluated for possible changes. To evaluate and minimize potential changes caused by the new processing software, the reprocessed data record was compared to the original data record archived in the World Ozone and UV Data Center (WOUDC) in Toronto, Canada. The history of the observations at the individual stations, the instruments used for the NOAA network monitoring at the station, the method for reducing zenith sky observations to total ozone, and calibration procedures were re-evaluated using data quality control tools built into the new software. At the completion of the evaluation, the new data sets are to be published as an update to the WOUDC and NDACC archives, and the entire data set is to be made available to the scientific community. The procedure for reprocessing Dobson data and the results of the re-analysis on the archived record is presented in this paper. A summary of historical changes to fourteen station records is also provided.

NOAA, through the Joint Polar Satellite System (JPSS) program, in partnership with the National Aeronautical and Space Administration, launched the Suomi National Polar-orbiting Partnership (S-NPP) satellite, a risk reduction and data continuity mission, on 28 October 2011. The JPSS program is executing the S-NPP Calibration and Validation program to ensure that the data products comply with the requirements of the sponsoring agencies. The Ozone Mapping and Profiler Suite (OMPS) consists of two telescopes feeding three detectors measuring solar radiance scattered by the Earth's atmosphere directly and solar irradiance by using diffusers. The measurements are used to generate estimates of total column ozone and vertical ozone profiles for use in near-real-time applications and extension of ozone climate data records. The calibration and validation efforts are progressing well, and both Level 1 (Sensor Data Records) and Level 2 (Ozone Environmental Data Records) have advanced to release at Provisional Maturity. This paper provides information on the product performance over the first 22 months of the mission. The products are evaluated through the use of internal consistency analysis techniques and comparisons to other satellite instrument and ground-based products. The initial performance finds total ozone showing negative bias of 2 to 4% with respect to correlative products and ozone profiles often within ±5% in the middle and upper stratosphere of current operational products. Potential improvements in the measurements and algorithms are identified. These will be implemented in coming months to reduce the differences further.

Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed to develop a mouse model to gain insight into the development of airway hyperresponsiveness (AHR) to methacholine (MCh) in mice after exposure to both allergen and ozone. Mice were exposed for 20 min per day for 10 consecutive days to an aerosol of 1% ovalbumin (OVA) or saline followed by a single 3-h exposure to clean air or 100, 250, or 500 ppb ozone. Ozone induced AHR in mice previously exposed to OVA when compared to non-exposed (saline) control mice. After a 10-d exposure to OVA, a single exposure to a low (100 ppb) ozone concentration was sufficient to induce AHR. The AHR response was associated with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice.

The technique of producing a vertical ozone profile using ground-based observations of the Umkehr effect is well established and is widely used for ozone trend analysis. Still, observations of the Umkehr effect by Dobson ozone spectrophotometers have a documented problem: simultaneous measurements from collocated instruments produce noticeably different results, with the difference shown to be dependent on solar zenith angle and total ozone. Ozone profiles are thus difficult to compare from station to station. Current investigations into the level and effects of stray light within the instrument suggest that much of the difference can be attributed to out-of-band stray light characteristics of individual Dobson instruments. Resulting changes in retrieved ozone profiles suggest that adjusting measurements for stray light components removes much of the existing bias between Umkehr profiles and other ozone measuring datasets. This new information has implications for both observational methods and completene...

The Dobson ozone spectrophotometer is the primary ground-based instrument making measurements of total column ozone. Knowledge of the ozone layer prior to the satellite measurements is derived from these instruments' more than 80-year record. Internal stray light within the instrument limits its ability to make accurate measurements at high total ozone amounts and high solar zenith angles (SZAs). Additionally, a recent analysis of comparative Dobson observations of the Umkehr effect (an SZA-dependent series of measurements on the clear zenith that are used to produce an ozone vertical profile) has shown that internal stray light produces incompatible results between compared instruments. We present a method of making a measurement of this internal stray light, as well as other approaches to evaluating the approximate level of the internal stray light. These techniques can also be used to improve the results of direct Sun observations at high latitudes and high ozone.

A comparison of retrieved total column ozone (TCO) amounts between the Pandora #34 spectrometer system and the Dobson #061 spectrophotometer from direct-sun observations was performed on the roof of the Boulder, Colorado, NOAA building. This paper, part of an ongoing study, covers a 1-year period starting on 17 December 2013. Both the standard Dobson and Pandora TCO retrievals required a correction, TCOcorr = TCO (1 + C(T)), using a monthly varying effective ozone temperature, TE, derived from a temperature and ozone profile climatology. The correction is used to remove a seasonal difference caused by using a fixed temperature in each retrieval algorithm. The respective corrections C(TE) are CPandora = 0.00333(TE-225) and CDobson = -0.0013(TE-226.7) per degree K. After the applied corrections removed most of the seasonal retrieval dependence on ozone temperature, TCO agreement between the instruments was within 1 % for clear-sky conditions. For clear-sky observations, both co-located instruments tracked the day-to-day variation in total column ozone amounts with a correlation of r2 = 0.97 and an average offset of 1.1 ± 5.8 DU. In addition, the Pandora TCO data showed 0.3 % annual average agreement with satellite overpass data from AURA/OMI (Ozone Monitoring Instrument) and 1 % annual average offset with Suomi-NPP/OMPS (Suomi National Polar-orbiting Partnership, the nadir viewing portion of the Ozone Mapper Profiler Suite).

Ozone is a highly reactive gas present in urban air, which penetrates deep into the lung and causes lung injury. The alveolar epithelial cells are among the first cell barriers encountered by ozone. To define the molecular basis of the cellular response to ozone, primary cultures of rat alveolar type II and type I-like cells were exposed to 100 ppb ozone or air for 1 h. The mRNA from both phenotypes was collected at 4 and 24 h after exposure for gene expression profiling. Ozone produced extensive alterations in gene expression involved in stress and inflammatory responses, transcription factors, antioxidant defenses, extracellular matrix, fluid transport, and enzymes of lipid metabolism and cell differentiation. Real-time reverse transcription-polymerase chain reaction and Western blot analysis verified changes in mRNA and protein levels of selected genes. Besides the increased stress response, ozone exposure downregulated genes of cellular differentiation. The changes were more prominent at 4 h in the type I-like phenotype and at 24 h in the type II phenotype. The type I-like cells were more sensitive to ozone than type II cells. The genome-wide changes observed provide insight into signal pathways activated by ozone and how cellular protection mechanisms are initiated.

Ozone exposure produces acute inflammation and neutrophil influx in the distal lung. Alveolar epithelial cells cover a large surface area, secrete chemokines, and may initiate or modify the inflammatory response. The effect of ozone on chemokine production by these cells has not been defined. Isolated rat type II cells were cultured in different conditions to express the morphologic appearance and biochemical markers for the type I and the type II cell phenotypes. These cells were exposed to ozone at an air/liquid interface. The type I-like cells were more susceptible to injury than the type II cells and showed signs of injury at exposure levels of 100 ppb ozone for 60 min. Both phenotypes showed evidence of lipid peroxidation after ozone exposure as measured by 8-isoprostane production, but neither phenotype secreted increased amounts of MIP-2 (CXCL3), CINC-1 (CXCL1), or MCP-1 (CCL2) in response to ozone. Both cell phenotypes secreted MIP-2 and MCP-1 in response to IL-1beta or lipopolysaccharide, but there was no priming or synergy with ozone. It is likely that the inflammatory response to ozone in the alveolar compartment is not due to the direct effect of ozone on epithelial cells.

The common air pollutant ozone causes acute toxicity to human airways. In primary and transformed epithelial cells from all levels of human or rat airways, ozone levels relevant to air pollution (50-200 ppb) increased extracellular [ATP] within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms electrically resistant polarized monolayers had up to 10-fold greater apical than basolateral surface extracellular [ATP] within 7 min of ozone exposure. Increased extracellular [ATP] appeared due to ATP secretion or release because (1) inhibition of ectonucleotidase (cell surface enzyme(s) which degrade ATP) by ozone did not occur until >120 min of ozone exposure and (2) brefeldin A, a secretory inhibitor, eliminated elevation of extracellular [ATP] without affecting intracellular ATP. Extracellular ATP protected against ozone toxicity in a P2Y receptor-dependent manner as (1) removal of ATP and adenosine by apyrase and adenosine deaminase, respectively, potentiated ozone toxicity, (2) extracellular supplementation with ATP, a poorly hydrolyzable ATP analog ATPgammaS, or UTP inhibited apoptotic and necrotic ozone-mediated cell death, and (3) ATP-mediated protection was eliminated by P2 and P2Y receptor inhibitors suramin and Cibacron blue (reactive blue 2), respectively. The decline in glucose uptake caused by prolonged ozone exposure was prevented by supplemental extracellular ATP, an effect blocked by suramin. Further, Akt and ERK phosphorylation resulted from exposure to supplemental extracellular ATP. Thus, extracellularly released ATP signals to prevent ozone-induced death and supplementation with ATP or its analogs can augment protection, at least in part via Akt and /or ERK signaling pathways and their metabolic effects.

Continuous measurements of total ozone (by Dobson spectrophotometers) across the contiguous United States (US) began in the early 1960s. Here, we analyze temporal and spatial variability and trends in total ozone from the five US sites with long-term records. While similar long-term ozone changes are detected at all five sites, we find differences in the patterns of ozone variability on shorter time scales. In addition to standard evaluation techniques, STL-decomposition methods (Seasonal Trend decomposition of time series based on LOcally wEighted Scatterplot Smoothing, LOESS) are used to address temporal variability and trends in the Dobson data. The LOESS-smoothed trend components show a decline of total ozone between the 1970s and 2000s and a "stabilization" at lower levels in recent years, which is also confirmed by linear trend analysis. Methods from statistical extreme value theory (EVT) are used to characterize days with high and low total ozone (termed EHOs and ELOs, respectively) at each station and to analyze temporal changes in the frequency of ozone extremes and their relationship to dynamical features such as the North Atlantic Oscillation and El Niño Southern Oscillation. A comparison of the "fingerprints" detected in the frequency distribution of the extremes with those for standard metrics (i.e., the mean) shows that more "fingerprints" are found for the extremes, particularly for the positive phase of the NAO, at all five US monitoring sites. Results from the STL-decomposition support the findings of the EVT analysis. Finally, we analyze the relative influence of low and high ozone events on seasonal mean column ozone at each station. The results show that the influence of ELOs and EHOs on seasonal mean column ozone can be as much as ±5%, or about twice as large as the overall long-term decadal ozone trends.

The dry deposition velocity of nitric acid, Vd(HNO3), over a 12-m (mean height) spruce–fir forest at Niwot Ridge, Colorado was estimated during 13 daytime periods using the flux-gradient approach. Turbulence intensity at this site is high (mean u ∗ of 0.65 m s−1 with u of 2.9 m s−1) and contributed to the large observed Vd(HNO3). The overriding contributor is identified to be the small aerodynamic needle width of the conifer trees. Two cases had inflated Vd(HNO3) due to height-differentiated nitric acid loss to soil-derived particle surfaces. Not considering these cases, the mean Vd(HNO3) was 7.6 cm s−1. The mean laminar boundary layer resistance (Rb) was found to be 7.8 s m−1 (of similar magnitude to that of the aerodynamic resistance, 8.5 s m−1). The data-determined Rb is bracketed by two theoretical estimates of the mean Rb, 5.9 and 8.6 s m−1, that include consideration of the small canopy length scale (aerodynamic needle width), 1 mm or less, at this conifer forest. However, the poor correlation of data-determined Rb values with both sets of theoretical estimates indicates that measurement error needs to be reduced and/or improved formulations of theoretical Rb values are in order. The large observed Vd(HNO3) at this conifer forest site is attributed to high turbulence intensity, and, especially, to small aerodynamic needle width.

Remote sounding methods are used to derive ozone profile and column information from various ground-based and satellite measurements. Vertical ozone profiles measured in Dobson units (DU) are currently retrieved based on laboratory measurements of the ozone absorption cross-section spectrum between 270 and 400 nm published in 1985 by Bass and Paur (BP). Recently, the US National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) proposed using the set of ozone cross-section measurements made at the Daumont laboratory in 1992 (BDM) for revising the Aura Ozone Monitoring Instrument (OMI) and Global Ozone Monitoring Experiment (GOME) satellite ozone profiles and total ozone column retrievals. Dobson Umkehr zenith sky data have been collected by NOAA ground-based stations at Boulder, CO (BDR) and Mauna Loa Observatory, HI (MLO) since the 1980s. The UMK04 algorithm is based on the BP ozone cross-section data. It is currently used for all Dobson Umkehr data processing submitted to the World Ozone and Ultraviolet radiation Data Centre (WOUDC) under the Global Atmosphere Watch (GAW) program of the World Meteorological Organization (WMO). Ozone profiles are also retrieved from measurements by the Mark IV Brewers operated by the NOAA-EPA Brewer Spectrophotometer UV and Ozone Network (NEUBrew) using a modified UMK04 algorithm (O3BUmkehr v.2.6, Martin Stanek). This paper describes the sensitivity of the Umkehr retrievals with respect to the proposed ozone cross-section changes. It is found that the ozone cross-section choice only minimally (within the retrieval accuracy) affects the Dobson and the Brewer Umkehr retrievals. On the other hand, significantly larger errors were found in the MLO and Boulder Umkehr ozone data (−8 and +5% bias in stratosphere and troposphere respectively) when the out-of-band (OOB) stray light contribution to the Umkehr measurement is not taken into account (correction is currently not included in the UMK04). The vertical distribution of OOB effect in the retrieved profile can be related to the local ozone climatology, instrument degradation, and optical characteristics of the instrument. Nonetheless, recurring OOB errors do not contribute to the long-term ozone trends.

Ozone is known to produce an acute influx of neutrophils, and alveolar epithelial cells can secrete chemokines and modulate inflammatory processes. However, direct exposure of alveolar epithelial cells and macrophages to ozone (O(3)) produces little chemokine response. To determine if cell-cell interactions might be responsible, we investigated the effect of alveolar macrophage-conditioned media after ozone exposure (MO(3)CM) on alveolar epithelial cell chemokine production. Serum-free media were conditioned by exposing a rat alveolar macrophage cell line NR8383 to ozone for 1 hour. Ozone stimulated secretion of IL-1alpha, IL-1beta, and IL-18 from NR8383 cells, but there was no secretion of chemokines or TNF-alpha. Freshly isolated type II cells were cultured, so as to express the biological markers of type I cells, and these cells are referred to as type I-like cells. Type I-like cells were exposed to diluted MO(3)CM for 24 hours, and this conditioned medium stimulated secretion of cytokine-induced neutrophil chemattractant-1 (CXCL1) and monocyte chemoattractant protein-1 (CCL2). Secretion of these chemokines was inhibited by the IL-1 receptor antagonist. Although both recombinant IL-1alpha and IL-1beta stimulated alveolar epithelial cells to secrete chemokines, recombinant IL-1alpha was 100-fold more potent than IL-1beta. Furthermore, neutralizing anti-rat IL-1alpha antibodies inhibited the secretion of chemokines by alveolar epithelial cells, whereas neutralizing anti-rat IL-1beta antibodies had no effect. These observations indicate that secretion of IL-1alpha from macrophages stimulates alveolar epithelial cells to secrete chemokines that can elicit an inflammatory response.

There is a qualitative understanding that gaseous elemental mercury (GEM) is oxidized during Arctic spring to reactive gaseous mercury (RGM) that afterwards is removed by fast deposition to snow surfaces. The conditional sampling or relaxed eddy accumulation (REA), technique represents the first opportunity to directly measure fluxes of reactive gaseous mercury (RGM) to the snow pack in the Arctic. Using a micrometeorological method REA system, with a heated sampling system specifically designed for Arctic use, the dry deposition of RGM is measured after polar sunrise, in Barrow, Alaska. Heated KCl-coated manual RGM annular denuders were used as the accumulators with an inlet allowing only fine particles to pass (Cut off diameter 2.5mm). At 3 m above the snow pack significant RGM fluxes were measured each spring in 2001–2004. Both depositions and emissions were observed. The emissions were attributed to chemical formation of RGM at or near the snow surface. The surface resistance, Rc, for RGM was found to be very small and set to zero as a first estimate. r 2006 Elsevier Ltd. All rights reserved.

Ozone (O3) can induce airway hyperresponsiveness (AHR) and neutrophilic inflammation. We evaluated the role of complement in development of AHR and inflammation after acute O3 exposure in mice. Mice were exposed to O3 at 2 ppm for 3 hours, and airway responsiveness to methacholine was measured 8 hours after O3 exposure. Complement was depleted or inhibited by intraperitoneal injection of cobra venom factor (CVF) or complement receptor-related gene y (Crry)-Ig, a potent C3 convertase inhibitor; neutrophils were depleted using an antineutrophil monoclonal antibody. CVF attenuated the development of AHR by O3. Administration of Crry-Ig also prevented the development of AHR. Bronchoalveolar lavage (BAL) fluid neutrophilia after O3 exposure was significantly decreased by administration of either CVF or Crry-Ig. Increased BAL fluid total protein after O3 exposure was lowered by depletion or inhibition of complement. In contrast to the effects of complement inhibition or depletion, depletion of BAL neutrophil counts by more than 90% with the monoclonal antibody did not affect the development of AHR after O3 exposure. These data indicated that activation of the complement system follows acute O3 exposure and is important to the development of AHR and airway neutrophilia. However, this neutrophil response does not appear necessary for the development of AHR.

Cell lines derived from non-small cell carcinomas of the lung (NSCLC) often express a variety of polypeptide growth factors able to activate receptors that encode tyrosine kinases. These receptors initiate numerous biological responses, including cell proliferation, and constitutive activation can result in cellular transformation. Consequently, it is possible that the aberrant growth properties of NSCLC cell lines is due at least in part to the action of mutated or perpetually activated receptor tyrosine kinases (RTK)s. As a first step in the process of testing this hypothesis we set out to examine the different RTKs expressed in NSCLC cell lines. A small group of NSCLC cell lines was screened for the expression of RTKs using a reverse transcriptase PCR approach with nested degenerate primers. We found four different RTKs expressed: the fibroblast growth factor receptor (FGFR) type III, the FGFR type IV, the platelet-derived growth factor beta receptor (beta PDGFR) and Flk-1/KDR, one of the receptors that binds vascular endothelial growth factor (VEGF). Since Flk-1/KDR and the beta PDGFR are not usually expressed in epithelial cells, we verified that they are expressed in NSCLC by Northern and Western blot analysis. To assess the incidence of expression of these RTKs in NSCLC cell lines a larger panel of cell lines was examined by Western blot analysis. The beta PDGFR was expressed in 30% (3/10) of the cell lines examined, while Flk-1/KDR was expressed in 10% (1/10). We also examined the expression of ligands for these RTKs. PDGF-A, PDGF-B and VEGF were expressed in 89%, 0% and 78%, respectively. While the high incidence of ligand expression made it likely that receptor and growth factor would be coexpressed, we found that in most instances this was not the case. Furthermore, in the cell lines in which the RTK and its ligand were coexpressed, we were unable to detect a functional autocrine loop. These studies indicate that while NSCLC cell lines aberrantly express various RTKs and growth factors, this does not always result in the establishment of an autocrine loop. These findings suggest that growth factors such as PDGF and VEGF act in a paracrine manner to contribute to the growth, survival and angiogenic program of a lung tumor.