抄録
Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood.We investigated whether CXCL12 regulate invasion into type I collagen and degradate of type I collagen. CXCL12 enhanced the invasion into type I collagen on NK cells. GM6001, a brode synthetic MMP inhibitor, significantly inhibited CXCL12-stimulated enhanced invasion. Furthermore, TIMP-2, recombinant tissue inhibitor of metalloproteinases, also significantly inhibited CXCL12-stimulated invasion into type I collagen. Fresh NK cells were incubated in the presence or absence of CXCL12 and plated on the DQ-collagen I, intramolecular-quenched fluorescent protein substrate, coated plates. CXCL12 stimulated cells significantly enhanced degradation of type I collagen on NK cells. This enhanced degradation was significantly inhibited by GM6001 or TIMP-2, although there was residual degradation of type I collagen.These results indicate that MMPs play a key role in CXCL12-stimulated NK cell invasion into type I collagen, and CXCL12 enhanced NK cell surface proteolysis of type I collagen in an MMP-dependent manner, thereby promoting NK cell invasion into the matrix. [J Physiol Sci. 2007;57 Suppl:S128]
