Abstract
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 that localization of MMP-1 and α2-Integrin on the surface of NK3.3 cells stimulated by CXCL12. CXCL12 enhanced the invasion into type I collagen on NK3.3 cells. GM6001 (a brode synthetic MMP inhibitor), TIMP-2 (recombinant tissue inhibitor of metalloproteinases) and Pertussis toxin (PTX: a smoll Gi protein inhibitor) significantly inhibited CXCL12-stimulated enhanced invasion. When NK cells were cultured in the presence of CXCL12, the production of MMP-1 was significantly enhanced compared with the unstimulated NK cells. To localize MMP-1 and α2 integrin subunit on NK-cell surface, NK cells cultured in the presence or absence of CXCL12 were stained with anti-MMP-1 antibody and anti-α2 integrin antibody. Although unstimulated NK cells expressed the majority of the MMP-1 colocalized with α2 integrin subunit around cell surface, stimulation with CXCL12 enhanced MMP-1 aggregation and colocalization with α2 integrin subunit on NK-cell surface. PTX significantly inhibited this aggregation.These results indicate that the CXCL12-stimulated NK cell invated into type I collagen, and this invasion involved in the aggregation of MMP-1 and α2 integrin subunit on NK-cell surface. [J Physiol Sci. 2008;58 Suppl:S202]
