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The calcium ionophore A23187 and anti-human IgE provoked a dose-dependent release of histamine and cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) from dispersed human lung cells. Optimal release of histamine peaked at 3 min after challenge whereas the release of cysteinyl-leukotrienes peaked at 30 min. The molar ratio between released histamine and cysteinyl-leukotrienes was approximately 100∶1. The ionophore, but not anti-IgE caused additional formation of LTB4 in the dispersed cells or the chopped lung, indicating that this chemoattractant is formed from cells not primarily activated by IgE-dependent mechanisms. Indomethacin failed to alter release of histamine or leukotrienes from dispersed cells, whereas further inhibition of lipoxygenases by NDGA abolished leukotriene formation and reduced the release of histamine.

Exogenous [3H]leukotriene B4(LTB4) was converted into several polar and non-polar metabolites in the chopped human lung. One of the major metabolites was identified as 5(S),12-dihydroxy-6,8,14-eicosatrienoic acid (10,11-dihydro-LTB4) by means of co-chromatography with authentic standards, ultraviolet spectrometry and gas chromatography-mass spectrometry. Analysis on chiral straight phase HPLC revealed the presence of both the 12(S) and 12(R) epimers of dihydro-LTB4. Dihydro-LTB4was also formed from endogenously generated LTB4in ionophore A23187 stimulated incubations. The dihydro metabolites were approximately 100 times less potent than LTB4in causing guinea pig lung strip contraction and leukocyte-dependent inflammation in the hamster cheek pouch in vivo.

Prostaglandin (PG)D"2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD"2, 9@a,11@b-PGF"2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9@a,11@b-PGF"2 in healthy volunteers. Morning baseline values of urinary 9@a,11@b-PGF"2 were measured in three groups-healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)-and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9@a,11@b-PGF"2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9@a,11@b-PGF"2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9@a,11@b-PGF"2, supporting dose-dependent release of PGD"2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9@a,11@b-PGF"2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9@a,11@b-PGF"2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo. (J ALLERGY CLIN IMMUNOL 1996;98:421-32.)

Wild and domestic populations of channel catfish Ictalurus punctatuswere examined to determine the distribution of the disease called enteric septicemia of catfish (ESC) in California. The causative agent of ESC, Edwardsiella ictaluri, was isolated from five separate sites in California. Two of these isolations were from rectal swabs of asymptomatic fish, confirming that a carrier state may exist. Normal-appearing fish with serum antibody titer to E. ictaluriwere commonly found in domestic channel catfish populations, suggesting that many fish become infected but recover. Wild channel catfish with antibody to E. ictaluriwere also found in major reservoirs and water distribution canals. Edwardsiella ictaluriappears to be widely distributed within California.

Abstract BackgroundAcute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. MethodsTen non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E ₄ (LTE ₄) and 9α,11β-PGF ₂, the earliest appearing urinary metabolite of prostaglandin D ₂ (PGD ₂), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. Results Methacholine PD ₂₀FEV ₁ decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p<0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and pre-challenge levels of LTE ₄ (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p<0.01) and 9α,11β-PGF ₂ (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p<0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB ₄ and LTE ₄ in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. Conclusions The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.

Background Leukotriene receptor antagonists significantly blunt allergen-induced bronchoconstriction in asthmatic subjects. Inhibitors of leukotriene synthesis should theoretically provide similar protection, but conflicting results have been obtained when synthesis inhibitors have been tested in allergen challenge. BAYx 1005, a new inhibitor of leukotriene synthesis, was therefore evaluated in an allergen bronchoprovocation study.Methods Ten men with mild allergic asthma and bronchial hyperresponsiveness to histamine were recruited. On two different occasions each subject inhaled a single dose of allergen, previously determined to cause at least a 20% fall in forced expiratory volume in one second (FEV₁) four hours after ingestion of 750 mg BAYx 1005 or placebo in a double blind crossover design. Urinary excretion of leukotriene E₄ was measured before and during the challenges.Results The mean (SE) maximal fall in FEV₁ was 7.1 (1.7)% after BAYx 1005 and 21.0 (3.0)% after placebo (p<0.001). The mean difference between treatments was 13.9 (95% CI 7.0 to 20.8) for the maximal fall in FEV₁. All subjects were protected by BAYx 1005, the mean inhibition of the fall in FEV₁ being 70.0 (7.0)%. The mean area under the curve (AUC) for urinary excretion of leukotriene E₄ in the first two hours after the challenge was 1.7 (0.9) after placebo and 0.4 (0.6) after BAYx 1005 (difference=1.3 (95% CI -0.1 to 2.7); p<0.05).Conclusions These results indicate that BAYx 1005 is a potent inhibitor of allergen-provoked leukotriene synthesis in asthmatic subjects and lend further support to the suggestion that leukotrienes are important mediators of allergen-induced bronchoconstriction.