MCP-1-STIMULATED MONOCYTE ATTACHMENT TO LAMININ IS MEDIATED BY BETA(2)-INTEGRINS

Migration of monocytes to sites of inflammation involves a series of a ttachments and detachments to extracellular matrix proteins. We examin ed the capacity of a chemokine, monocyte chemoattractant protein-1 (MC P-1), to regulate attachment of human monocytes to laminin, collagen I , collagen TV, or fibronectin. MCP-1 increased monocyte attachment to laminin in a dose- and time-dependent manner and stimulated a lesser i ncrease to the other matrix proteins. Function-blocking monoclonal ant ibodies (MAbs) to the integrin beta(2)-subunit (CD18), including Fab' fragments and alpha(M) (CD11b) blocked > 70% of attachment, whereas MA bs to the beta(1)-integrin subunit reduced attachment by <30%. This su ggests that the CD11b/CD18 integrin is the predominant molecule involv ed in adhesion of MCP-l-stimulated monocytes to laminin. The associati on of CD11b with F-actin illustrated by confocal microscopy further su pports this concept. In contrast, when monocytes were stimulated with the beta(1)-stimulatory MAb TS2/16, monocyte adhesion to laminin occur red through beta(1)-integrins. Thus MCP-1 can stimulate monocyte attac hment to laminin, and this process is mediated through beta(2)-integri ns, principally CD11b/CD18.