Protease phenotype of constitutive connective tissue and of induced mucosal mast cells in mice is regulated by the tissue

Abstract

Mouse mast cells (MCs) express a large number of serine proteases including tryptases, mouse mast cell protease (mMCP)-6 and -7; chymases, mMCP-1, -2, and -4; and an elastase, mMCP-5; along with carboxypeptidase-A3 (CPA3). In helminth-infected mouse intestine, distinct protease phenotypes are observed for connective tissue MCs (CTMCs) (mMCP-4 + -7 + , and CPA3 + ) and mucosal MCs (MMCs) (mMCP-1 + and 2 + ). To determine whether the protease phenotype was regulated by the tissue, we compared the phenotype of constitutive CTMCs and induced MMCs in trachea and large airways in antigen-sensitized unchallenged and challenged mice to MCs in skin and helminthic-infected intestine. We found that in the trachea, unlike in skin and intestine, CTMCs and MMCs both express all six serine proteases and CPA3 (mMCP-1 ). This phenotype also holds for the lung CTMCs in the proximal bronchi, whereas the induced MMCs express only four proteases, mMCP-1, -2, -6, and -7. Thus, the T-cell-dependent induction of MMCs in trachea, large bronchi, and small intestine provides numbers but does not determine the protease phenotype. Furthermore, the CTMCs, which are constitutive, also show striking differences at these tissue sites, supporting the view that the differences in expression are tissue directed and not dependent on inflammation.

Heparan Sulfate 6-O-Sulfotransferase Isoform-dependent Regulatory Effects of Heparin on the Activities of Various Proteases in Mast Cells and the Biosynthesis of 6-O-Sulfated Heparin

“…6A). Such expression profiles of the chymase genes in WT-FSMCs are consistent with those in CTMCs (22,24). Expression of the mRNAs of the major chymases in FSMCs, mMCP-4 and mMCP-5, was analyzed by quantitative RT-PCR (Fig.…”

“…Mast cells (MCs) are classified into connective tissue-type mast cells (CTMCs) and mucosal mast cells (22). Each mast cell type is differentiated by the types of glycosaminoglycans and MC-specific proteases present and is involved in a variety of physiological and pathological processes (23)(24)(25)(26)(27)(28)(29)(30).…”

Two Functionally Distinct Subsets of Mast Cells Discriminated By IL-2–Independent CD25 Activities

“…Indeed, the protease repertoire of mast cells was strongly influenced by the surrounding host tissue (6), and Trichinella spiralis infection led to the identification of hypogranular mast cells that could be an important source of cytokines during helminth infection (7). Potentially, other mast cell subsets with different characteristics, possibly tailored to and determined by the local environment of a given tissue or inflammatory status, await description.…”

Epicutaneous Sensitization Results in IgE-Dependent Intestinal Mast Cell Expansion and Food Anaphylaxis

“…3,10 Following oral challenge, mice EC sensitized with OVA exhibited a significant decrease in core body temperature (Fig. 1C), and significantly elevated serum levels of the β-chymase mMCP-1expressed in mucosal MCs 8,11,12 compared to controls EC sensitized with saline (Fig. 1D).…”