scholarly journals Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

2006 ◽  
Vol 176 (2) ◽  
pp. 899-904 ◽  
Author(s):  
Alan D. Pemberton ◽  
Steven H. Wright ◽  
Pamela A. Knight ◽  
Hugh R. P. Miller
1995 ◽  
Vol 182 (6) ◽  
pp. 1871-1881 ◽  
Author(s):  
C L Scudamore ◽  
E M Thornton ◽  
L McMillan ◽  
G F Newlands ◽  
H R Miller

The soluble granule chymase, rat mast cell protease-II (RMCP-II), is abundantly expressed in intestinal mucosal mast cells (MMC) but its function is not known. One hypothesis is that RMCP-II degrades the epithelial basement membrane and promotes the loss of enterocytes typically associated with type I hypersensitivity reactions in the rat. To test this hypothesis more directly, ex vivo perfusion of the cranial mesenteric artery and jejunal lumen was used to monitor the anaphylactic release of RMCP-II and its effects on mucosal permeability and epithelial integrity. Within 2 min of intravascular challenge with soluble adult Nippostrongylus brasiliensis worm antigen there was a 1,000-fold (P < 0.02) increase in the concentration of RMCP-II in the vascular perfusate from the jejunum of Nippostrongylus-sensitized rats but not the controls. Similarly, translocation of RMCP-II into the gut lumen increased 10-fold (P < 0.02) after 2 min only in worm antigen-challenged immune rats. Using an identical protocol, but incorporating Evans blue-labeled human serum albumin (EB-HSA) in the vascular perfusate, the timing of the release of RMCP-II into the two compartments was very similar to the first experiment and furthermore the translocation of EB-HSA increased 18-fold (P < 0.05) after 4 min in sensitized rats challenged with worm antigen. To examine the effects of RMCP-II more directly 1 mg of the highly purified chymase was introduced into the cranial mesenteric artery in ex vivo perfused normal rats. A significant (P < 0.05) 70-fold increase in concentration of RMCP-II in jejunal perfusate occurred after 6 min. In a repeat dose-response experiment, infusion of 0.375, 0.75, or 1.5 mg of RMCP-II, together with EB-HSA, established that the cumulative amounts of RMCP-II and EB-HSA translocated from the vasculature to the gut lumen in each perfusion (during the 10-min period of RMCP-II infusion) were significantly correlated. Analysis of intestinal perfusates by SDS-PAGE and by Western blotting using monoclonal anti-RMCP-II antibody confirmed that there was a concomitant translocation of both the protease and EB-HSA into the gut lumen. Histological evaluation of the mucosa failed to reveal any significant morphological change in any of the experiments. The rapid development of macromolecular leak, its association with the translocation of RMCP-II, and the absence of gross epithelial lesions, suggest for the first time that a mast cell granule chymase increases epithelial permeability via a paracellular route and implies that the substrate may be a protein, or proteins, in the epithelial junctional complex.


2000 ◽  
pp. 257-273 ◽  
Author(s):  
Pamela A. Knight ◽  
Steven H. Wright ◽  
Elisabeth M. Thornton ◽  
Jeremy Brown ◽  
Hugh R.P. Miller

2003 ◽  
Vol 33 (1) ◽  
pp. 132-146 ◽  
Author(s):  
J. K. Brown ◽  
P. A. Knight ◽  
S. H. Wright ◽  
E. M. Thornton ◽  
H. R. P. Miller

2000 ◽  
Vol 68 (9) ◽  
pp. 4968-4971 ◽  
Author(s):  
Denis N. Onah ◽  
Fukumi Uchiyama ◽  
Yuuko Nagakui ◽  
Masao Ono ◽  
Toshiyuki Takai ◽  
...  

ABSTRACT A possible role for the γ subunit of immunoglobulin Fc receptors (FcR) in mucosal defenses against intestinal nematode parasites was studied using age-matched FcRγ-knockout (FcRγ−/−) and wild-type (FcRγ+/+) C57BL/6 mice. Mice were infected subcutaneously with 3,000 infective larvae of Strongyloides venezuelensis, and the degree of infection was monitored by daily fecal egg counts and adult worm recovery on days 8 and 13 postinfection. Mucosal mast cell (MMC) responses were assayed by in situ intestinal mast cell counts in stained histological sections of the jejunum and by measuring mouse mast cell protease 1 (MMCP-1) release in serum using sandwich enzyme-linked immunosorbent assay. FcRγ−/− mice had significantly higher egg counts (P < 0.01) and numbers of adult worms (P < 0.05) than FcRγ+/+mice, but mastocytosis and serum MMCP-1 release were comparable. It was concluded that MMCP-1 release may be spontaneous, does not depend on mast cell degranulation via the FcRγ signaling system, and appears to play no role in the expulsion of S. venezuelensis. The delay in worm expulsion in the FcRγ−/− mice might be related to inability of the MMC to degranulate and release effector molecules other than MMCP-1, since FcRγ deletion abrogates mast cell degranulative responses.


1990 ◽  
Vol 96 (6) ◽  
pp. 857-863 ◽  
Author(s):  
Michael S. Kaminer ◽  
Robert M. Lavker ◽  
Laurence J. Walsh ◽  
Diana. Whitaker ◽  
Burton. Zweiman

2013 ◽  
Vol 346 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Martin Houde ◽  
Marc-David Jamain ◽  
Julie Labonté ◽  
Louisane Desbiens ◽  
Gunnar Pejler ◽  
...  

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