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Expression of metalloproteinase‐7 (matrilysin) in human blood and bronchoalveolar Gamma/Delta T‐lymphocytes. Selective upregulation by the soluble non‐peptidic mycobacterial phosphoantigen (isopentenyl pyrophosphate)
Author(s) -
Workalemahu Grefachew,
Foerster Martin,
Kroegel Claus
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20541
Subject(s) - matrilysin , isopentenyl pyrophosphate , biology , matrix metalloproteinase , microbiology and biotechnology , bronchoalveolar lavage , downregulation and upregulation , immunology , immune system , antigen , western blot , immunohistochemistry , enzyme , medicine , gene , biochemistry , biosynthesis , lung
Human γδ T‐lymphocytes are believed to regulate local immune defense and enhance resistance against invading microbes, although their precise function remains unknown. Herein, we addressed the question whether γδ T‐lymphocytes mediate these processes via synthesis of MMP‐7, a protease closely associated with both epithelial repair and mucosal defense. Blood and bronchoalveolar γδ T‐lymphocytes were cultured in the absence and presence of isopentenyl pyrophosphate (IPP) or TGF‐β1/IL‐15 for 24 h, and assessed for the expression and synthesis of MMP‐1, MMP‐7, and MMP‐9. Resting human γδ T‐lymphocytes constitutively expressed MMP‐9 mRNA, a marginal or no MMP‐7 and MMP‐1 mRNA. In the presence of IPP (3 µg/ml), expression of MMP‐7 mRNA significantly increased, whereas TGF‐β1/IL‐15 had no effect. Further, quiescent γδ T‐lymphocytes obtained from bronchoalveolar lavage (BAL) fluid showed a weak or no MMP‐7 mRNA signal which was raised significantly following stimulation with IPP. In Western blot analysis, a 28‐kDa pro‐matrilysin could be detected both in cell lysates (2 days) and supernatants (5 days) with a four‐ to sevenfold increased signal following IPP‐stimulation of the γδ T‐lymphocytes. In conclusion, the data demonstrate for the first time that both human blood and BAL γδ T‐lymphocytes express MMP‐7 mRNA and synthesize MMP‐7‐protein. This unfolds a new perspective for the understanding of γδ T‐lymphocyte function. J. Cell. Physiol. 207: 67–74, 2006. © 2005 Wiley‐Liss, Inc.