Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules: Relevance for leukocyte extravasation

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Abstract

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 β2-integrins play an indisputable role in adhesion of polymorphonuclear granulocytes (PMN) to endothelium, we show here that β1- and β3-integrins but not β2-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 β2-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 β2-integrin null PMN showed the same pattern of ECM binding, indicating that β2-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 α5β1 and αvβ3, respectively; to laminin 10 via α6β1; 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 α6β1, a major laminin receptor, demonstrating that expression of α6β1 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 β2-integrins are not essential for such interactions.

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Sixt, M., Hallmann, R., Wendler, O., Scharffetter-Kochanek, K., & Sorokin, L. M. (2001). Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules: Relevance for leukocyte extravasation. Journal of Biological Chemistry, 276(22), 18878–18887. https://doi.org/10.1074/jbc.M010898200

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