Abstract

Mast cells (MCs) are highly specialized immune cells present in mammals and in lower organisms that predate the development of adaptive immunity. The strong evolutionary pressure to retain MCs for >500 million years suggests critical roles for these cells in our survival. In support of this conclusion, no human has been identified to date that lacks MCs, despite the adverse roles of MCs in systemic anaphylaxis and varied inflammatory disorders. MCs express numerous lineage-restricted neutral proteases, and four members of the chromosome 17A3.3 family of tryptases are preferentially expressed in mouse MCs. The anatomical location of MCs at host-environment interfaces has raised the possibility that some of these enzymes are evolutionally conserved because they are needed for combating infectious organisms. Here we review recent insights into the structure and function of MC tryptases in inflammation and host defense against bacteria and other infectious organisms.

Highlights

  • Mast cells (MCs) are highly specialized immune cells present in mammals and in lower organisms that predate the development of adaptive immunity

  • The proteases packaged in the secretory granules of mouse MCs include carboxypeptidase A3 (CPA3), granzyme B, cathepsin G, neuropsin, transmembrane tryptase/tryptase ␥/protease serine member S (Prss) 31, mouse MC protease 1–10, and mMCP-11/Prss34

  • Because of the loss of fully sulfated heparin, the MCs in the skin and peritoneal cavities of NDST-2-null mice store reduced amounts of mMCP-6 and almost no CPA3, mMCP-4, and mMCP-5, even though all four MC-restricted protease genes are transcribed at normal rates

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Summary

Expression of Tryptase Genes in MCs

All mouse strains examined to date express mMCP-6. In contrast, mMCP-7 and Prss are expressed in strain-dependent manners [18, 27, 28]. Prss is considerably more abundant in the MCs of C57BL/6J mice than those of BALB/cJ and 129/SvJ mice [18] These three MC tryptases can be differentially expressed within specific tissues of the same mouse strain. The safraninϩ MCs in the skin of BALB/cJ mice contain abundant amounts of mMCP-6 and mMCP-7, whereas the safraninϩ MCs in the peritoneal cavity of this mouse strain express mMCP-6 but not mMCP-7 [29]. The intestines of C57BL/6J mice contain more Prss than mMCP-6 or mMCP-7 [15] These three tryptase family members are not coordinately expressed in mouse MCs even though their genes are adjacent to one another on chromosome 17A3.3. Information on the expression of hPrss is limited, but the MCs in the intestine, skin, and airway submucosa store this tryptase in their secretory granules [15, 18, 20]

Structural Analysis of MC Tryptases
Bioactivity and Substrate Preferences of MC Tryptases
Findings
MC Tryptases in Bacterial Infections
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