BIDIRECTIONAL INDUCTION OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE-1 DURING T-LYMPHOMA ENDOTHELIAL-CELLCONTACT - IMPLICATION OF ICAM-1
F. Aoudjit et al., BIDIRECTIONAL INDUCTION OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE-1 DURING T-LYMPHOMA ENDOTHELIAL-CELLCONTACT - IMPLICATION OF ICAM-1, The Journal of immunology, 160(6), 1998, pp. 2967-2973
The mechanisms that lead to the expression of matrix metalloproteinase
s (MMP) and tissue inhibitors of MMP (TIMPs) during the invasive proce
ss of normal and transformed T cells remain largely unknown. Since vas
cular cells form a dynamic tissue capable of responding to local stimu
li and activating cells through the expression of cytokine receptors a
nd specific cell adhesion molecules, we hypothesized that the firm adh
esion of T lymphoma cells to endothelial cells is a critical event in
the local production of MMP and TIMP. In the present work, we show tha
t adhesion of lymphoma cells to endothelial cells induced a transient
and reciprocal de novo expression of MMP-9 mRNA and enzymatic activity
by both cell types, Up-regulation of MMP-9 in T lymphoma cells was co
ncomitant to that of TIMP-1, and required direct contact with endothel
ial cells, Induction of MMP-9, but not of TIMP-1, was blocked by anti-
LFA-1 and anti-intercellular adhesion molecule-1 Abs, indicating that
induction of MMP-9 and TIMP-1 in lymphoma cells required direct, yet d
istinct, intercellular contact, In contrast, the induction of MMP-9 in
endothelial cells by T lymphoma cells did not necessitate direct cont
act and could be achieved by exposure to IL-1 and TNF, or to the super
natant of T lymphoma cell culture, Together, these results demonstrate
that firm adhesion of T lymphoma cells to endothelial cells participa
tes in the production of MMP-9 in both cell types through bi-direction
al signaling pathways, and identify intercellular adhesion molecule-1/
LFA-1 as a key interaction in the up-regulation of MMP-9 in T lymphoma
cells.