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Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close apposition. We examined interactions between primary cultured MMC and CGRP-IR DRG neurons in vitro by confocal recording of intracellular Ca2+ concentration ([Ca2+]i). The degranulatory EC50 for the mast cell secretagogue compound 48/80 (C48/80; 10 µg/ml) and the neuropeptides CGRP (2.10-8 M) and substance P (SP; 3.10-8 M) were determined by measurement of extracellular release of the granule chymase, mouse mast cell protease-1. Application of C48/80 (10 µg/ml) and CGRP and SP (both 10-7 M) to Fluo-4-loaded MMC induced a transient rise in [Ca2+]i after a lag time, indicative of mast cell degranulation and/or secretion. The CGRP response could be completely blocked by pertussis toxin (2 µg/ml), indicating involvement of Gi proteins. Application of MMC juice, obtained by C48/80 degranulation of MMC, to Fluo-4-loaded DRG neurons induced in all neurons a rise in [Ca2+]i, indicative of activation. Degranulation of MMC by C48/80 in culture dishes containing Fluo-4-1oaded DRG neurons also caused activation of the DRG neurons. In conclusion, these results demonstrate a bidirectional cross-talk between cultured MMC and CGRP-IR DRG neurons in vitro. This indicates that such a communication may be the functional relevance for the close apposition between MMC and CGRP-IR nerve fibers in vivo. [ABSTRACT FROM AUTHOR]

The systemic secretion of rat mucosal mast cell protease (RMCPII) was examined in Nippostrongylus-primed rats injected intravenously with N. brasiliensis whole worm antigen. The secretory response in primed rats was both time- and dose-dependent whereas no RMCPII was present in the sera of naive rats challenged with antigen, RMCPII was detected in the sol and gel phases of intestinal perfusates, the release of enzyme into the gut lumen occurring very rapidly after challenge in immune rats. Mucosal permeability, assessed by measuring the passage of Evan's blue from the blood into the gut lumen was both time- and dose-dependent and reflected the combined capillary and epithelial permeability. Although the release of RMCPII into the gut lumen occurred more rapidly than the intraluminal accumulation of Evan's blue, these two events were highly correlated. There were, in addition significant correlations between the systemic and enteric secretion of RMCPII and the enteric accumulation of Evan's blue. These results indicate that RMCPII may have a role in altering intestinal mucosal permeability during systemic anaphylaxis in the rat. [ABSTRACT FROM AUTHOR]

The expression of granule proteinases by murine bone marrow-derived mast cells (BMMC) grown in vitro was compared with that of serosal mast cells (SMC) from the peritoneal cavity. The granules in a proportion of BM MC (0.4-13%) and in all SM C were labelled with fluorescent antibodies against rat mast cell protease I (RMCP I). The granules of 1-47% of BMMC and 100% of SMC were labelled with antibodies against a 30,000 molecular weight (MW) murine intestinal mast cell proteinase (MIMCP). Four antigens from BMMC, ranging in MW from 28,000 to 32,000 and a single 28,000 antigen from SMC were detected on Western blot using anti-MIMCP antibodies. Only the 28,000 MW antigens from BMMC and SMC were visualized in blots probed with anti-RMCP 1. BMMC grown in the presence of conditioned medium from activated splenocytes or from the WEH1-3B myelomonocytic cell line contained 52-118 ng and 3-25 ng MIMCP/106 cells respectively, whereas SMC lacked detectable MIMCP. The selective labelling of the 28,000 MW antigens in BMMC and SMC with anti-RMCP I and the variable expression of this antigen in BMMC as detected by immunofluorescence indicates that BMMC are not a homogeneous population of cells. [ABSTRACT FROM AUTHOR]

Measurement of the mast cell response in the jejunal mucosae of rats infected with Nippostrongylus brasiliensis was carried out at the time of worm expulsion (self-cure). Just prior to the start of self-cure, a new mast cell population differentiated from cells with large nuclei and prominent nucleoli. Beginning on the 10th day of infection, mast cell numbers increased in an exponential fashion and reached a peak in the middle of the self-cure reaction 14 days after infection. At first the cells had few granules but their granule content subsequently increased and by day 14 some of them appeared to be mature. Mitoses were observed in granulated cells at all stages of the population expansion. Differential counts showed that an increasing proportion of the mast cell population migrated intraepithelially to become globule leucocytes so that by day 14 the ratio of globule leucocytes to mast cells was 1/1. On subsequent days of infection, this ratio and the total population of granulated cells gradually diminished. The results suggest that cell differentiation and division are responsible for the population increase. The high globule leucocyte/mast cell ratio points to an extensive release of amines from the granules during self-cure. The significance of this reaction in relation to antibody release from the mucosa and to worm expulsion is discussed. [ABSTRACT FROM AUTHOR]

Both differentiating plasma cells and modified lymphocytes (lympho-plasmocytes) synthesize specific humoral antibody in rabbits, rats, mice and guinea-pigs. They do so during both primary and secondary responses, after subcutaneous injection of three enzymic antigens: horse radish peroxidase, glucose oxidase and alkaline phosphatase, administered as soluble or insolubilized proteins or alum precipitated or mixed with Freund's adjuvant. [ABSTRACT FROM AUTHOR]