scholarly journals The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 925 ◽  
Author(s):  
Zhiqiang Li ◽  
Dimitra Peirasmaki ◽  
Staffan Svärd ◽  
Magnus Åbrink

Mast cells have been shown to affect the control of infections with the protozoan parasite Giardia intestinalis. Recently, we demonstrated that Giardia excretory-secretory proteins inhibited the activity of the connective tissue mast cell-specific protease chymase. To study the potential role of the chymase mouse mast cell protease (mMCP)-4 during infections with Giardia, mMCP-4+/+ and mMCP-4−/− littermate mice were gavage-infected with G. intestinalis trophozoites of the human assemblage B isolate GS. No significant changes in weight gain was observed in infected young (≈10 weeks old) mMCP-4−/− and mMCP-4+/+ littermate mice. In contrast, infections of mature adult mice (>18 weeks old) caused significant weight loss as compared to uninfected control mice. We detected a more rapid weight loss in mMCP-4−/− mice as compared to littermate mMCP-4+/+ mice. Submucosal mast cell and granulocyte counts in jejunum increased in the infected adult mMCP-4−/− and mMCP-4+/+ mice. This increase was correlated with an augmented intestinal trypsin-like and chymotrypsin-like activity, but the myeloperoxidase activity was constant. Infected mice showed a significantly lower intestinal neutrophil elastase (NE) activity, and in vitro, soluble Giardia proteins inhibited human recombinant NE. Serum levels of IL-6 were significantly increased eight and 13 days post infection (dpi), while intestinal IL-6 levels showed a trend to significant increase 8 dpi. Strikingly, the lack of mMCP-4 resulted in significantly less intestinal transcriptional upregulation of IL-6, TNF-α, IL-25, CXCL2, IL-2, IL-4, IL-5, and IL-10 in the Giardia-infected mature adult mice, suggesting that chymase may play a regulatory role in intestinal cytokine responses.

Life Sciences ◽  
2013 ◽  
Vol 93 (25-26) ◽  
pp. e57
Author(s):  
Martin Houde ◽  
Walid Semaan ◽  
Louisane Desbiens ◽  
Zhipeng You ◽  
Adel G. Schwertani ◽  
...  

2001 ◽  
Vol 107 (2) ◽  
pp. 315-321 ◽  
Author(s):  
Hae-Ki Min ◽  
Naotomo Kambe ◽  
Lawrence B. Schwartz

1993 ◽  
Vol 294 (1) ◽  
pp. 127-135 ◽  
Author(s):  
G F J Newlands ◽  
D P Knox ◽  
S R Pirie-Shepherd ◽  
H R P Miller

Five highly soluble, chymotrypsin-like, neutral serine proteases, with molecular masses in the range 30-33 kDa, were isolated from Trichinella spiralis-infected mouse small intestine. These enzymes were closely related antigenically on Western blotting and by Ouchterlony double diffusion using a polyclonal, cross-absorbed, sheep antibody raised against mouse mast cell protease-1 (MMCP-1) and on the basis of N-terminal amino acid sequence analysis, were identified as variant forms of MMCP-1. Substrate and inhibitor analysis confirmed that the five variants (MMCP-1 A-E) had similar characteristics, although highly significant (P = 0.025 to P < 0.0001) variations in Km and kcat, were detected. Against human alpha 1-proteinase inhibitor the Ki for MMCP-1C (45 pM) was significantly (P < 0.0001) greater than those for the other proteases (0.76-2.2 pM). The differences in electrophoretic mobility are probably a result of variable glycosylation, since removal of N-linked carbohydrate produced a polypeptide of approx. 28 kDa in each case which was, like the native enzyme, immunoreactive on Western blotting. A much less soluble 28 kDa enzyme was isolated from serosal mast cells and identified as MMCP-4 by N-terminal amino acid sequencing. Like MMCP-1 it has chymotrypsin-like substrate specificities with activity at neutral pH. However, it was antigenically distinct from MMCP-1 and, using sheep anti-MMCP-1, was not detected on Western blotting or by Ouchterlony double diffusion, e.l.i.s.a. or immunohistochemistry. This last technique established that the MMCP-1 variants were uniquely present in enteric mast cells, thereby providing a highly selective means of distinguishing the mucosal and connective tissue mast cell subsets in the mouse.


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.


2018 ◽  
Vol 9 ◽  
Author(s):  
Martin Houde ◽  
Adel Schwertani ◽  
Hanène Touil ◽  
Louisane Desbiens ◽  
Otman Sarrhini ◽  
...  

2019 ◽  
Vol 1865 (6) ◽  
pp. 1170-1181 ◽  
Author(s):  
Yunzhe Wang ◽  
Cong-Lin Liu ◽  
Wenqian Fang ◽  
Xian Zhang ◽  
Chongzhe Yang ◽  
...  

2003 ◽  
Vol 302 (4) ◽  
pp. 773-777 ◽  
Author(s):  
Kayo Saito ◽  
Tsuyoshi Muto ◽  
Yoshiaki Tomimori ◽  
Seiichi Imajo ◽  
Hiroshi Maruoka ◽  
...  

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