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Matrix Metalloproteinase-1 Produced by Human CXCL12-Stimulated Natural Killer Cells

Authors
Journal
American Journal Of Pathology
0002-9440
Publisher
Elsevier
Publication Date
Volume
169
Issue
2
Identifiers
DOI: 10.2353/ajpath.2006.050676
Keywords
  • Matrix Pathobiology
Disciplines
  • Biology
  • Medicine

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. In this study, we show that CXCL12 significantly enhanced CD16 +CD56 + human peripheral NK-cell invasion into type I collagen by the catalytic activity of matrix metalloproteinase-1 (MMP-1). Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with α 2β 1 integrin on CXCL-12-stimulated NK-cell surface. The binding of pro-MMP-1 with α 2β 1 integrin required activation of G i-coupled pathway. However, the production of MMP-1 from CXCL12-stimulated NK cells was mediated by p38 and mitogen-activated or extracellular signal-regulation protein kinase kinase 1/2 in a manner independent of the G i-coupled pathway. These results suggest that CXCL12/CXCR4 interaction transduces the two signaling pathways to promote NK-cell invasion, which stimulates pericellular degradation of extracellular matrix proteins by membrane-associated MMP-1. The mechanisms would thus play a role in facilitating lymphocyte trafficking and accumulation in tissues during physiological and pathological processes.

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