Direct contact between T lymphocytes and monocytes is a major pathway for induction of metalloproteinase expression.
Monocytes and macrophages can modulate the turnover of extracellular matrix by producing metalloproteinases such as interstitial collagenase and 92-kDa gelatinase as well as tissue inhibitor of metalloproteinases. To study mechanisms of metalloproteinase induction in human mononuclear phagocytes, the effects of direct cell-cell contact between activated T lymphocytes and the human monocytic cell line THP-1 were determined. T cells were first activated with phorbol 12-myristate 13-acetate and phytohemagglutinin for 24 h, fixed with paraformaldehyde, and then exposed to THP-1 cells for 48 h. Upon contact with fixed activated T lymphocytes, a massive induction in the expression of both proteinases and tissue inhibitor of metalloproteinases was observed, whereas unstimulated T cells had no effect. Stimulation of metalloproteinase biosynthesis by THP-1 cells was mimicked by a membrane preparation derived from activated T cell lines, whereas cytosol and nuclear fractions of the T cells were ineffective. Furthermore, activated T lymphocytes exposed to trypsin, tunicamycin, or cycloheximide lost the capacity to stimulate THP-1 cells upon subsequent contact, implying the involvement of cell-surface glycoproteins. Similar induction of metalloproteinases by direct contact with activated T cells was also observed using normal blood monocytes as the target cells, and stimulation of monocyte metalloproteinases by T cell contact occurs at a pretranslational level. Consequently, cell-cell contact may represent an important biological mechanism for potentiating the inflammatory response that leads to extracellular matrix destruction.
Lacraz
S
S
Department of Medicine, University Hospital, Geneva, Switzerland.
Isler
P
P
Vey
E
E
Welgus
H G
HG
Dayer
J M
JM
D002450:Cell Communication; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004790:Enzyme Induction; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009000:Monocytes / Q000166:cytology / Q000201:enzymology*; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology*
D016207:Cytokines; D008562:Membrane Glycoproteins; D008666:Metalloendopeptidases