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)

J Cell Physiol. 2006 Apr;207(1):67-74. doi: 10.1002/jcp.20541.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Gene Expression / drug effects
  • Hemiterpenes / pharmacology*
  • Humans
  • Integrin alpha Chains / genetics
  • Interleukin-15 / pharmacology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Organophosphorus Compounds / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Antigens, CD
  • Hemiterpenes
  • Integrin alpha Chains
  • Interleukin-15
  • Organophosphorus Compounds
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • alpha E integrins
  • isopentenyl pyrophosphate
  • Matrix Metalloproteinase 7
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1