Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by the tryptase mouse mast cell protease 6 (mMCP-6)

R. L. Stevens, D. S. Friend, W. T. Qiu, G. W. Wong, G. Morales, J. Hunt, C. Huang

Research output: Contribution to journalArticle

Abstract

Recombinant mMCP-6 was generated to study the role of this tryptase in inflammatory reactions. Seven to 48 h after the i.p. injection of mMCP-6 into BALB/c, mast cell-deficient WCB6F1-S1/Sld, Co-deficient, or mMCP-5-null mice, the number of neutrophils in the peritoneal cavity of each animal increased >50 fold. The failure of the closely related recombinant tryptase mMCP-7 to induce a comparable peritonitis indicated that the substrate specificities of the two tryptases are very different. Unlike most forms of acute inflammation, the mMCP-6-mediated-peritonitis was relatively long lasting and neutrophil specific. mMCP-6 did not induce neutrophil chemotaxis directly in an in vitro assay but did promote chemotaxis of the leukocyte in the presence of endothelial cells. mMCP-6 did not induce cultured endothelial cells to express TNF-alpha, RANTES, IL-1, or IL-6, but did induce these cells to express large amounts of IL-8 continually over a 40-h time period. Neither enzymatically active mMCP-7 nor enzymatically inactive pro-mMCP-6 were able to induce endothelial cells to increase their expression of IL-8. The finding that mMCP-6 selectively induces cultured human endothelial cells to release large amounts of IL-8 now raises the possibility that this tryptase regulates the steady-state levels of a neutrophil- specific chemokine in vivo during mast cell-mediated inflammatory events.

Original languageEnglish (US)
Pages (from-to)A894
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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