ISSN:
1365-2222
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Mucosal mast cells (MMC) play a central role in gut hypersensitivities and inflammation. They are morphologically, biochemically and functionally distinct from their connective tissue counterparts. Massive hyperplasia of MMC occurs 7–10 days after intestinal infection with nematodes but it has never been possible to replicate this phenomenon in vitro.〈section xml:id="abs1-2"〉〈title type="main"〉Objective(1) To determine whether mouse bone marrow-derived mast cells (mBMMC) grown in the presence of transforming growth factor (TGF)-β1 could develop over the same time frame (7–10 days) as MMC in parasitized mice. (2) To compare the early expression of surface receptors (integrins αE and β7, c-kit and FcεR) with that of the MMC-specific granule chymase mouse mast cell protease-1 (mMCP-1).〈section xml:id="abs1-3"〉〈title type="main"〉MethodsMouse bone marrow cells were cultured in the presence of IL-9, IL-3 and Stem Cell Factor (SCF) with or without TGF-β1. mBMMC were quantified after toluidine blue or Leishmans' staining. Expression of MMC-specific mouse mast cell proteases was analysed by ELISA, immunohistochemistry and RT-PCR. Surface antigen expression was characterized by flow cytometry and confocal microscopy.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsTGF-β1 promotes the development of abundant MMC-like mBMMC from bone marrow progenitor cells with kinetics, which closely parallel that seen in vivo. mRNA transcripts encoding mMCP-1 and -2 are readily detectable by day 4 ex vivo in cultures grown in the presence of TGF-β1. Between 30 and 40% and 75–90% of the cells in these cultures on days 4 and 7, respectively, have typical mast cell morphology, are c-kit+, FcεR+, integrin αEβ7+, and express and secrete abundant mMCP-1. The integrin αE subunit is coexpressed with mMCP-1.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionThe kinetics of mMCP-1+/αE+ mBMMC development, regulated by TGF-β1, are consistent with that seen in vivo in the parasitized intestine. The normally down-regulatory functions of TGF-β1 in haematopoiesis are superseded in this culture system by its ability to promote the early expression of αE and mMCP-1.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2222.2002.01233.x
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