title: Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha.
abstract: Mast cells, essential effector cells in allergic inflammation, have been found to be activated in T cell-mediated inflammatory processes in accordance with their residence in close physical proximity to T cells. We have recently reported that mast cells release granule-associated mediators and TNF-alpha upon direct contact with activated T cells. This data suggested an unrecognized activation pathway, where mast cells may be activated during T cell-mediated inflammation. Herein, we show that this cell-cell contact results in the release of matrix metalloproteinase (MMP)-9 and the MMP inhibitor tissue inhibitor of metalloproteinase 1 from HMC-1 human mast cells or from mature peripheral blood-derived human mast cells. The expression and release of these mediators, as well as of beta-hexosaminidase and several cytokines, were also induced when mast cells were incubated with cell membranes isolated from activated, but not resting, T cells. Subcellular fractionation revealed that the mature form of MMP-9 cofractionated with histamine and tryptase, indicating its localization within the secretory granules. MMP-9 release was first detected at 6 h and peaked at 22 h of incubation with activated T cell membranes, while TNF-alpha release peaked after only 6 h. Anti-TNF-alpha mAb inhibited the T cell membrane-induced MMP-9 release, indicating a possible autocrine regulation of MMP release by mast cell TNF-alpha. This cascade of events, whereby mast cells are activated by T cells to release cytokines and MMP-9, which are known to be essential for leukocyte extravasation and recruitment to affected sites, points to an important immunoregulatory function of mast cells within the context of T cell-mediated inflammatory processes.
authors.affiliation: Department of Medicine, Meir General Hospital, Kfar-Saba, 44281 Israel.
authors.forename: D
authors.initials: D
authors.lastname: Baram
authors.forename: G G
authors.initials: GG
authors.lastname: Vaday
authors.forename: P
authors.initials: P
authors.lastname: Salamon
authors.forename: I
authors.initials: I
authors.lastname: Drucker
authors.forename: R
authors.initials: R
authors.lastname: Hershkoviz
authors.forename: Y A
authors.initials: YA
authors.lastname: Mekori
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication; D002478:Cells, Cultured; D017364:Collagenases / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004792:Enzyme Precursors / Q000032:analysis; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D001619:beta-N-Acetylhexosaminidases / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D004792:Enzyme Precursors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D001619:beta-N-Acetylhexosaminidases; D017364:Collagenases; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9