Matrix Metalloproteinase-1 Produced by Human CXCL8 - Activated NK Cells

Abstract

Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL8 is one of the chemokines that promote leukocytes invasion and migration into tissues, while the exact molecular mechanisms are not clear at present. In this study, we showed that CXCL8 significantly enhanced CD16⁺CD56⁺ human peripheral NK cells invasion into type I collagen by the catalytic activity of MMP-1. MMP-1 inhibitor, GM6001 and Gi-protein inhibitor, PTX blocked the invasion of CD16⁺CD56⁺ human peripheral NK cells into type I collagen. GM6001 and PTX did not inhibit the production of MMP-1 in CD16⁺CD56⁺ human peripheral NK cells. PTX inhibited the association of MMP-1 but not GM6001, with cell surface in CXCL-8 in CD16⁺CD56⁺ human peripheral NK cells. The association of MMP-1 with cell surface on CXCL-8-stimulated NK cells suggests that this integrin plays a role not in promoting cell migration to type I collagen but cell invasion into type I collagen. These results suggest that the selective regulations of production and/or localization of MMP-1 in NK cells may lead to effective strategies to control inflammation and tumor elimination.