[beta]2-integrins preferentially mediate monocyte chemoattractant protein-1
(mcp-1) induced monocyte migration on extracellular matrix proteins.
Penberthy, Timothy W., Yanling Jiang, Francis W. Luscinskas, and Dana T.
Graves.
Division of Oral Biology, Boston University School of Graduate Dentistry,
Department of Biochemistry, Boston University School of Medicine, Boston, MA
02118. Vascular Research Division, Departments of Pathology, Brigham and
Women's Hospital and Harvard Medical School, Boston, MA 02115
APStracts 2:0059C, 1995.
Recruitment of monocytes to inflammatory sites involves a series of sequential
attachments and detachments to extracellular matrix proteins in response to a
chemoattractant gradient. In this study we compared the migration of human
peripheral blood monocytes on different extracellular matrix proteins in
response to monocyte chemoattractant protein-1 (MCP-1) and fMLP. Monocytes
migrated more effectively on laminin as compared to other extracellular
matrix proteins. In contrast, this preference was not observed with neutro
phils, suggesting that the monocytes and neutrophils may have differences in
their migration on extracellular matrix proteins. To study this further,
function-blocking monoclonal antibodies were used to examine mechanistically
whether [beta]1-and [beta]2-integrins were involved in monocyte migration on
fibrone ctin or laminin in response to MCP-1. Monocyte migration on both
laminin and fibronectin was blocked 100% (p<0.05) by intact monoclonal
antibody, F(ab') fragments, and F(ab')2 fragments to [beta]2-integrins. We
also determined that antibodies to [beta]2-integrins block monocyte migration
that has already been initiated. In contrast, antibody to the [beta]1-
integrins inhibited monocyte migration by approximately 40% (p<0.05). Thus,
monocytes which express both [beta]1-and [beta]2-integrins require utilization
of [beta]2-integrins in migration on extracellular matrix proteins. The
results also suggest that [beta]-1 integrins facilitate monocyte migration but
that monocyte migration is not absolutely dependent upon the interaction of
[beta]1-integrins with extracellular matrix proteins. In contrast, neutrophil
migration is [beta]2-integrin dependent and is not facilitated by [beta]1-
integrins.
Received 18 October 1994; accepted in final form 4 January 1995.
APS Manuscript Number C621-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 27 February 1995.