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Hematopoietic Serine Proteases: Important Players in Inflammation and Tissue Homeostasis - 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 2960

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Guest Editor
Department of Cell and Molecular Biology, Uppsala University BMC, Box 596, SE-751 24 Uppsala, Sweden
Interests: mast cells; basophilic leukocytes, neutrophilic leukocytes; serine proteases; cleavage specificity; phage display; IgE; evolution; allergy; vaccines; Fc receptors; dermatitis; cytokines; immune regulation
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Special Issue Information

Dear Colleagues,

Several of the hematopoietic cell lineages store massive amounts of serine proteases in cytoplasmic secretory granules. These proteases, which can account for up to 35% of the total cellular protein, are stored in an active form, ready for rapid release upon cell activation. In mammals, these proteases are expressed primarily by mast cells, neutrophils, cytotoxic T cells, and NK cells and they are encoded from four different chromosomal loci. Known functions involve activation of apoptosis in target cells, inducing cytokine production, regulating blood pressure, inactivating snake and scorpion toxins, regulating coagulation, regulating cytokine activity as well as participating in tissue homeostasis. Some of them are very active and have a relatively broad specificity and thereby many potential targets, whereas others are highly specific with only one or a few selected targets. Although much is known about these proteases, very much remains unknown. A few examples of important unsolved questions are: why do mast cells continuously produce such high amounts of these proteases; another is the major target for one of the recently identified highly specific neutrophil proteases (NSP4); and what is the prime function of the most highly conserved members of this subfamily of serine proteases (the granzymes A and K)? This Special Issue will try to address some of these important outstanding questions in the area of hematopoietic serine proteases.

Prof. Lars Hellman
Guest Editor

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Keywords

  • serine protease
  • cleavage specificity
  • mast cell
  • neutrophilic granulocyte
  • cytotoxic T cell
  • NK cell
  • immune regulation
  • toxin
  • tissue homeostasis
  • angiotensin
  • cytokines

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Published Papers (1 paper)

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Review

26 pages, 12247 KiB  
Review
The Evolutionary History of the Chymase Locus -a Locus Encoding Several of the Major Hematopoietic Serine Proteases
by Srinivas Akula, Zhirong Fu, Sara Wernersson and Lars Hellman
Int. J. Mol. Sci. 2021, 22(20), 10975; https://doi.org/10.3390/ijms222010975 - 11 Oct 2021
Cited by 12 | Viewed by 2310
Abstract
Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases [...] Read more.
Several hematopoietic cells of the immune system store large amounts of proteases in cytoplasmic granules. The absolute majority of these proteases belong to the large family of chymotrypsin-related serine proteases. The chymase locus is one of four loci encoding these granule-associated serine proteases in mammals. The chymase locus encodes only four genes in primates, (1) the gene for a mast-cell-specific chymotryptic enzyme, the chymase; (2) a T-cell-expressed asp-ase, granzyme B; (3) a neutrophil-expressed chymotryptic enzyme, cathepsin G; and (4) a T-cell-expressed chymotryptic enzyme named granzyme H. Interestingly, this locus has experienced a number of quite dramatic expansions during mammalian evolution. This is illustrated by the very large number of functional protease genes found in the chymase locus of mice (15 genes) and rats (18 genes). A separate expansion has also occurred in ruminants, where we find a new class of protease genes, the duodenases, which are expressed in the intestinal region. In contrast, the opossum has only two functional genes in this locus, the mast cell (MC) chymase and granzyme B. This low number of genes may be the result of an inversion, which may have hindered unequal crossing over, a mechanism which may have been a major factor in the expansion within the rodent lineage. The chymase locus can be traced back to early tetrapods as genes that cluster with the mammalian genes in phylogenetic trees can be found in frogs, alligators and turtles, but appear to have been lost in birds. We here present the collected data concerning the evolution of this rapidly evolving locus, and how these changes in gene numbers and specificities may have affected the immune functions in the various tetrapod species. Full article
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