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).
Human gammadelta 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 gammadelta T-lymphocytes mediate these processes via synthesis of MMP-7, a protease closely associated with both epithelial repair and mucosal defense. Blood and bronchoalveolar gammadelta T-lymphocytes were cultured in the absence and presence of isopentenyl pyrophosphate (IPP) or TGF-beta1/IL-15 for 24 h, and assessed for the expression and synthesis of MMP-1, MMP-7, and MMP-9. Resting human gammadelta T-lymphocytes constitutively expressed MMP-9 mRNA, a marginal or no MMP-7 and MMP-1 mRNA. In the presence of IPP (3 microg/ml), expression of MMP-7 mRNA significantly increased, whereas TGF-beta1/IL-15 had no effect. Further, quiescent gammadelta 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 gammadelta T-lymphocytes. In conclusion, the data demonstrate for the first time that both human blood and BAL gammadelta T-lymphocytes express MMP-7 mRNA and synthesize MMP-7-protein. This unfolds a new perspective for the understanding of gammadelta T-lymphocyte function.
Workalemahu
Grefachew
G
University Medical Clinic I, Pneumology & Allergology/Immunology, Jena, Germany.
Foerster
Martin
M
Kroegel
Claus
C
D015703:Antigens, CD / Q000235:genetics; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D045782:Hemiterpenes / Q000494:pharmacology*; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics; D019409:Interleukin-15 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D015703:Antigens, CD; D045782:Hemiterpenes; D039001:Integrin alpha Chains; D019409:Interleukin-15; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C091367:alpha E integrins; C004809:isopentenyl pyrophosphate; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1