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Systemic release of mucosal mast-cell protease in primed rats challenged with Nippostrongylus brasiliensis
Abstract:
The systemic secretion of a serine protease, rat mast-cell protease II (RMCPII), a major product of rat mucosal mast cells (MMC), was measured by a sensitive enzyme-linked immunosorbent assay (ELISA) in the sera of naive and primed rats challenged with the nematode N. brasiliensis. The systemic secretion of RMCPII was both time- and dose-dependent in primed rats (1-3 micrograms RMCPII/ml serum, 1 hr after challenge). Systemic release of RMCPII was slower and less pronounced in naive rats following intraduodenal challenge with 5-day-old worms. No RMCPII was detected in the sera of naive rats challenged with 4-day-old N. brasiliensis. Soluble worm antigen had no effect in naive rats, but when it was given intraduodenally or intravenously to primed rats, the serum levels of RMCPII 1 hr later were 10.5 micrograms/ml and 122 micrograms/ml, respectively. Few morphological changes were detected in MMC following worm challenge and the jejunal content of RMCPII was unaltered. A substantial reduction in the number of MMC occurred following intravenous injection of worm antigen, and the remaining cells were vacuolated and pale-staining, although granule exocytosis was not observed. Significant reduction in the jejunal content of RMCPII was also evident. These results demonstrate, unequivocally, that MMC are activated in response to N. brasiliensis challenge infection or to parasite antigens. In addition, the ability to detect secreted RMCPII in the sera of test animals provides a highly sensitive and uniquely selective assay to determine the participation of MMC in pathological reactions at mucosal surfaces.
Insights
Systemic secretion of rat mast-cell protease II (RMCPII) indicates mucosal mast cell (MMC) activation during N. brasiliensis infection. Measuring RMCPII in serum offers a sensitive assay for MMC involvement in mucosal reactions.
Area of Science:
- Immunology
- Parasitology
- Biochemistry
Background:
- Mucosal mast cells (MMC) are key players in immune responses at mucosal surfaces.
- Rat mast-cell protease II (RMCPII) is a major secretory product of MMC.
- Nematode infections, such as N. brasiliensis, are known to elicit mast cell responses.
Purpose of the Study:
- To measure the systemic secretion of RMCPII in rats challenged with N. brasiliensis.
- To assess the utility of serum RMCPII levels as a marker for MMC activation.
- To investigate the effect of parasite antigens on MMC and RMCPII levels.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to quantify serum RMCPII levels.
- Rats were either naive or primed and challenged with N. brasiliensis worms or soluble worm antigen.
- RMCPII levels in serum and jejunal content were measured at various time points.
Main Results:
- Systemic RMCPII secretion was time- and dose-dependent in primed rats following N. brasiliensis challenge.
- Primed rats showed significantly higher serum RMCPII levels after challenge or antigen exposure compared to naive rats.
- Intravenous administration of worm antigen to primed rats resulted in a marked increase in serum RMCPII and a reduction in jejunal MMC and RMCPII.
- Morphological changes in MMC and jejunal RMCPII content were observed, indicating activation and degranulation.
Conclusions:
- MMC are unequivocally activated in response to N. brasiliensis infection and parasite antigens.
- Serum RMCPII detection provides a sensitive and selective assay for evaluating MMC participation in mucosal pathologies.
- This study validates RMCPII as a biomarker for MMC activation in parasitic infections.