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

Chifu Huang, Daniel S. Friend, Wen Tao Qiu, Guang W. Wong, Guillermo Morales, John Hunt, Richard L. Stevens

Research output: Contribution to journalArticlepeer-review

Abstract

Recombinant mouse mast cell protease 6 (mMCP-6) was generated to study the role of this tryptase in inflammatory reactions. Seven to forty-eight hours after the i.p. injection of recombinant mMCP-6 into BALB/c, mast cell- deficient WCB6F1-Sl/Sl(d), C5-deficient, or mMCP-5-null mice, the number of neutrophils in the peritoneal cavity of each animal increased significantly by > 50-fold. The failure of the closely related recombinant tryptase mMCP-7 to induce a comparable peritonitis indicates 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. Mouse MCP-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. Mouse MCP-6 did not induce cultured human endothelial cells to express TNF-α, RANTES, IL-1α, or IL-6. However, the tryptase induced endothelial cells to express large amounts of IL-8 continually over a 40-h period. Neither enzymatically active mMCP-7 nor enzymatically inactive pro-mMCP-6 was able to induce endothelial cells to increase their expression of IL-8. Although the mechanism by which mMCP-6 induces neutrophil accumulation in tissues remains to be determined, the finding that mMCP-6 induces cultured human endothelial cells to selectively release large amounts of IL-8 raises the possibility that this tryptase regulates the steady state levels of neutrophil-specific chemokines in vivo during mast cell-mediated inflammatory events.

Original languageEnglish (US)
Pages (from-to)1910-1919
Number of pages10
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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