Cell adhesion and migration properties of beta 2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation.
Regulated adhesion of leukocytes to the extracellular matrix is essential for transmigration of blood vessels and subsequent migration into the stroma of inflamed tissues. Although beta(2)-integrins play an indisputable role in adhesion of polymorphonuclear granulocytes (PMN) to endothelium, we show here that beta(1)- and beta(3)-integrins but not beta(2)-integrin are essential for the adhesion to and migration on extracellular matrix molecules of the endothelial cell basement membrane and subjacent interstitial matrix. Mouse wild type and beta(2)-integrin null PMN and the progranulocytic cell line 32DC13 were employed in in vitro adhesion and migration assays using extracellular matrix molecules expressed at sites of extravasation in vivo, in particular the endothelial cell laminins 8 and 10. Wild type and beta(2)-integrin null PMN showed the same pattern of ECM binding, indicating that beta(2)-integrins do not mediate specific adhesion of PMN to the extracellular matrix molecules tested; binding was observed to the interstitial matrix molecules, fibronectin and vitronectin, via integrins alpha(5)beta(1) and alpha(v)beta(3), respectively; to laminin 10 via alpha(6)beta(1); but not to laminins 1, 2, and 8, collagen type I and IV, perlecan, or tenascin-C. PMN binding to laminins 1, 2, and 8 could not be induced despite surface expression of functionally active integrin alpha(6)beta(1), a major laminin receptor, demonstrating that expression of alpha(6)beta(1) alone is insufficient for ligand binding and suggesting the involvement of accessory factors. Nevertheless, laminins 1, 8, and 10 supported PMN migration, indicating that differential cellular signaling via laminins is independent of the extent of adhesion. The data demonstrate that adhesive and nonadhesive interactions with components of the endothelial cell basement membrane and subjacent interstitium play decisive roles in controlling PMN movement into sites of inflammation and illustrate that beta(2)-integrins are not essential for such interactions.
Interdisciplinary Center for Clinical Research and the Institute for Experimental Medicine, Nikolaus Fiebiger Center, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
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M
Sixt
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Hallmann
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O
Wendler
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Scharffetter-Kochanek
L M
LM
Sorokin
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D018821:CD18 Antigens / Q000096:biosynthesis*; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004727:Endothelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009504:Neutrophils / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D016622:Silver Staining; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
D018821:CD18 Antigens; D005353:Fibronectins; D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin; D008024:Ligands; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D019096:Vitronectin; C119013:laminin 10; C110308:laminin 8; C047981:arginyl-glycyl-aspartic acid