Author:
Hellman Lars,Thorpe Michael
Abstract
Abstract
Cells from several of the hematopoietic cell lineages including mast cells, basophils, neutrophils, cytotoxic T cells, and natural killer (NK) cells store proteases at very high levels within their cytoplasmic granules. In mast cells, these proteases can account for up to 35% of the total cellular protein, and the absolute majority of these belong to the chymotrypsin-related serine protease family. A number of very diverse functions have been identified for these proteases, including apoptosis induction, blood pressure regulation, inactivation of insect and snake toxins, intestinal parasite expulsion, killing of bacteria and fungi, induction, mobilization, or degradation of cytokines, and the degradation of connective tissue components. A very broad spectrum of primary cleavage specificities has also been observed, including chymase, tryptase, asp-ase, elastase, and met-ase specificities, which highlights the large flexibility in the active site of these proteases. Mast cells primarily express chymases and tryptases with chymotryptic or tryptic primary cleavage specificities, respectively. Neutrophils have several enzymes with chymase, elastase, and tryptase specificities. T cells and NK cells express between 5 and 14 different granzymes, depending on the species, and these enzymes have tryptase, asp-ase, chymase, and met-ase specificities. This review focuses on the appearance of these proteases during vertebrate evolution, their primary and extended cleavage specificities, and their potential in vivo substrates. The in vivo substrates and functions are a particular challenging issue because several of these enzymes have a relatively broad specificity and may therefore cleave a wide range of different substrates.
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
Reference416 articles.
1. new allele sash at the locus and a spontaneous recessive lethal in mice;Lyon;Genet Res,1982
2. cells protect mice fromMycoplasma pneumonia;Xu;Am Crit Care Med,2006
3. Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss - of - function mutations;Trivedi;Allergy Clin Immunol,2009
4. Extended substrate specificity of rat mast cell protease a rodent α - chymase with elastase - like primary specificity;Karlson;Biol Chem,2003
5. Essential role for mast cell tryptase in acute experimental colitis;Hamilton;Proc Natl Acad Sci USA,2011
Cited by
49 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献