@article {529371,
	title = {Role of αLβ2 integrin avidity in transendothelial chemotaxis of mononuclear cells},
	journal = {J. Immunol.},
	volume = {159},
	number = {8},
	year = {1997},
	note = {Supported by grant$\#$ CA31798Reprint Status: In File},
	pages = {3968-3975},
	abstract = {The leukocyte integrin alpha L beta 2 (LFA-1) is important in transendothelial migration. Since it is not fully understood how LFA-1 mediates transmigration, we studied the effects of alpha L and beta 2 cytoplasmic domain mutants that alter LFA-1 adhesiveness for intercellular adhesion molecule-1. Monocyte chemotactic protein-1 (MCP-1) induced LFA-1-dependent transendothelial migration of Jurkat and J-beta 2.7 transfectants coexpressing the MCP-1 receptor CCR2B and wild-type alpha L. No transendothelial chemotaxis was observed with truncation mutants of the alpha L cytoplasmic tail, which rendered LFA-1 constitutively active or locked LFA-1 in a low avidity state unresponsive to cellular activation. Moreover, transendothelial chemotaxis of lymphoblastoid SLA transfectants was abolished by truncation of the beta 2 cytoplasmic domain, but not by mutation of its TTT motif, which is important in phorbol ester-induced adhesion. These data indicate that transmigration may require both alpha L and beta 2 cytoplasmic domains. We further show that MCP-1-induced transendothelial chemotaxis of PBMC was inhibited by sustained activation of LFA-1 with Mn2+ or a stimulatory mAb to beta 2. Dimeric soluble intercellular adhesion molecule-1 also reduced transendothelial chemotaxis of PBMC. Taken together, our data suggest that transendothelial chemotaxis of mononuclear cells may involve dynamic changes in LFA-1 avidity.},
	author = {Weber,C. and Lu,C-F. and Casasnovas,J.M. and Springer, T.A.}
}
