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5
1 Integrins Reverses the Inhibitory Effect of Tenascin on Chemotaxis of Human Monocytes and Polymorphonuclear Leukocytes Through Three-Dimensional Gels of Extracellular Matrix Proteins1
*
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032; and
Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425
Tenascin is an extracellular matrix protein found in adults in T
cell-dependent areas of lymphoid tissues, sites of inflammation, and
tumors. We report here that it inhibited chemotaxis of
chemoattractant-stimulated human monocytes and
chemoattractant-stimulated polymorphonuclear leukocytes (PMN) through
three-dimensional gels composed of collagen I or Matrigel, and
chemotaxis of leukotriene B4-stimulated PMN through
fibrin gels. The inhibitory effect of tenascin on monocyte or PMN
chemotaxis through these matrices was reversed by Abs directed against
5
1 integrins or by a peptide (GRGDSP)
that binds to 1 integrins. Tenascin did not affect
leukotriene B4- or fMLP-stimulated expression of
1 or 2 integrins, but did exert a small
inhibitory effect on PMN adhesion and closeness of apposition to
fibrin(ogen)-containing surfaces. Thus,
51 integrins mediate the inhibitory
effect of tenascin on monocyte and PMN chemotaxis, without promoting
close apposition between these leukocytes and surfaces coated with
tenascin alone or with tenascin bound to other matrix proteins. This
contrasts with the role played by 51
integrins in promoting close apposition between fMLP-stimulated PMN and
fibrin containing surfaces, thereby inhibiting chemotaxis of
fMLP-stimulated PMN through fibrin gels. Thus, chemoattractants and
matrix proteins regulate chemotaxis of phagocytic leukocytes by at
least two different mechanisms: one in which specific chemoattractants
promote very tight adhesion of leukocytes to specific matrix proteins
and another in which specific matrix proteins signal cessation of
migration without markedly affecting strength of leukocyte
adhesion.
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