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.