Transforming growth factor-bβ1 mediates coexpression of the integrin subunit aαE and the chymase mouse mast cell protease-1 during the early differentiation of bone marrow-derived mucosal mast cell homologues

2002 ◽  
Vol 32 (2) ◽  
pp. 315-324 ◽  
Author(s):  
S. H. Wright ◽  
J. Brown ◽  
P. A. Knight ◽  
E. M. Thornton ◽  
P. J. Kilshaw ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mucosal Mast Cell ◽  
Integrin Subunit ◽  
Early Differentiation ◽  
Mast Cell Protease ◽  
Mouse Mast Cell

A Novel Function for Transforming Growth Factor-β1: Upregulation of the Expression and the IgE-Independent Extracellular Release of a Mucosal Mast Cell Granule-Specific β-Chymase, Mouse Mast Cell Protease-1

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3473-3486 ◽  
Author(s):  
Hugh R.P. Miller ◽  
Steven H. Wright ◽  
Pamela A. Knight ◽  
Elisabeth M. Thornton
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Mast Cells ◽  
Culture Supernatant ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Extracellular Release ◽  
Mouse Mast Cell ◽  
Tgf Β1

Intestinal mucosal mast cells (IMMC) express granule neutral proteases that are regulated by T-cell–derived cytokines, including interleukin-3 (IL-3) and IL-9, and by stem cell factor (SCF). The IMMC-specific chymase, mouse mast cell protease-1 (mMCP-1), is released in substantial quantities into the blood stream during gastrointestinal allergic responses. We used cultured bone marrow-derived mast cells (mBMMC) to identify cytokines that regulate the expression and extracellular release of mMCP-1. When grown in IL-3–rich WEHI (15% vol/vol) and 50 ng/mL recombinant rat SCF (rrSCF) bone marrow cells supplemented with IL-9 (5 ng/mL) differentiated into mBMMC that expressed a maximum of less than 250 ng mMCP-1/106 cells and 189 ng mMCP-1/mL of culture supernatant. Supplementation of the same three cytokines with transforming growth factor-β1(TGF-β1; 1 ng/mL) resulted in substantially enhanced expression (6 μg/106 mBMMC) and extracellular release (2 μg/mL of culture supernatant) of mMCP-1. The response to TGF-β1 was dose-dependent, with maximal effect at 1 ng/mL, and was associated with immunohistochemical and ultrastructural changes in the secretory granules. IL-9–induced expression of mMCP-1 may be due to endogenously expressed TGF-β1, because it was blocked by anti–TGF-β antibodies. In conclusion, the expression and extracellular release of the IMMC-specific chymase, mMCP-1, is strictly regulated by TGF-β1.

Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-β and activin in mast cell progenitors

2005 ◽  
Vol 17 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Masayuki Funaba ◽  
Teruo Ikeda ◽  
Masaru Murakami ◽  
Kenji Ogawa ◽  
Matanobu Abe
Keyword(s):  
Mast Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mast Cell Protease ◽  
Mouse Mast Cell

Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

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
Keyword(s):  
Mast Cell ◽  
Mucosal Mast Cell ◽  
Mast Cell Protease ◽  
Constitutive Secretion ◽  
Mouse Mast Cell

scholarly journals Mucosal Defense against Gastrointestinal Nematodes: Responses of Mucosal Mast Cells and Mouse Mast Cell Protease 1 during PrimaryStrongyloides venezuelensis Infection in FcRγ-Knockout Mice

2000 ◽  
Vol 68 (9) ◽  
pp. 4968-4971 ◽  
Author(s):  
Denis N. Onah ◽  
Fukumi Uchiyama ◽  
Yuuko Nagakui ◽  
Masao Ono ◽  
Toshiyuki Takai ◽  
...  
Keyword(s):  
Mast Cell ◽  
Gastrointestinal Nematodes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mucosal Mast Cell ◽  
Mast Cell Protease ◽  
Intestinal Nematode ◽  
Nematode Parasites ◽  
Cell Counts ◽  
Strongyloides Venezuelensis ◽  
Mouse Mast Cell

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.

scholarly journals Delayed Expulsion of the Nematode Trichinella spiralisIn Mice Lacking the Mucosal Mast Cell–Specific Granule Chymase, Mouse Mast Cell Protease-1

2000 ◽  
Vol 192 (12) ◽  
pp. 1849-1856 ◽  
Author(s):  
Pamela A. Knight ◽  
Steven H. Wright ◽  
Catherine E. Lawrence ◽  
Yvonne Y.W. Paterson ◽  
Hugh R.P. Miller
Keyword(s):  
Mast Cell ◽  
Serine Proteases ◽  
Trichinella Spiralis ◽  
Gastrointestinal Nematodes ◽  
Intestinal Lumen ◽  
Mucosal Mast Cell ◽  
Mast Cell Protease ◽  
Muscle Larvae ◽  
Mouse Mast Cell

Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The β-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific β-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1−/− BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.

scholarly journals Mouse bone marrow-derived mast cells (mBMMC) obtained in vitro from mice that are mast cell-deficient in vivo express the same panel of granule proteases as mBMMC and serosal mast cells from their normal littermates.

1994 ◽  
Vol 180 (1) ◽  
pp. 67-73 ◽  
Author(s):  
K K Eklund ◽  
N Ghildyal ◽  
K F Austen ◽  
D S Friend ◽  
V Schiller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Steady State ◽  
Mast Cells ◽  
Induced Expression ◽  
Mast Cell Protease ◽  
Steady State Levels ◽  
Mouse Mast Cell

The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F1/J-W/Wv (W/Wv) and WCB6F1/J-Sl/Sld (Sl/Sld) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB-(+/+), WC-(+/+), W/Wv, and Sl/Sld mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-(+/+), WC-(+/+), and W/Wv mice. That Sl/Sld and W/Wv mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10-induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-(+/+) mBMMC and W/Wv mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-(+/+) and W/Wv mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4.

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