J. Exp. Med., Volume 187, Number 12, June 15, 1998 2091-2096

₁ Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo

By Joachim Werr,^* Xun Xie,^* Per Hedqvist,^* Erkki Ruoslahti, and Lennart Lindbom^*

From the ^* Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden; and  The Burnham Institute, La Jolla, California 92037

Recruitment of leukocytes from blood to tissue in inflammation requires the function of specific cell surface adhesion molecules. The objective of this study was to identify adhesion molecules that are involved in polymorphonuclear leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10⁷ M). Intravital time-lapse videomicroscopy was used to analyze migration velocity of the activated PMNs, and the modulatory influence on locomotion of locally administered antibodies or peptides recognizing various integrin molecules was examined. Immunofluorescence flow cytometry revealed increased expression of ₄, ₁, and ₂ integrins on extravasated PMNs compared with blood PMNs. Median migration velocity in response to PAF stimulation was 15.5 ± 4.5 µm/min (mean ± SD). Marked reduction (67 ± 7%) in motility was observed after treatment with mAb blocking ₁ integrin function (VLA integrins), whereas there was little, although significant, reduction (22 ± 13%) with ₂ integrin mAb. Antibodies or integrin-binding peptides recognizing ₄₁, ₅₁, or _v3 were ineffective in modulating migration velocity.

Our data demonstrate that cell surface expression of ₁ integrins, although limited on blood PMNs, is induced in extravasated PMNs, and that members of the ₁ integrin family other than ₄₁ and ₅₁ are critically involved in the chemokinetic movement of PMNs in rat extravascular tissue in vivo.

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