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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1804-1809
Integrin  2 1 (VLA-2) is a principal
receptor used by neutrophils for locomotion in extravascular tissue
Joachim Werr,
Joakim Johansson,
Einar E. Eriksson,
Per Hedqvist,
Erkki Ruoslahti, and
Lennart Lindbom
Department of Physiology and Pharmacology, Karolinska Institutet,
Stockholm, Sweden; The Burnham Institute, La Jolla, CA
92037.
Cell adhesion molecules are critically involved in the
multistep process of leukocyte recruitment in inflammation. The
specific receptors used by polymorphonuclear leukocytes (PMN) for
locomotion in extravascular tissue have as yet not been identified. By
means of immunofluorescence flow cytometry and laser scanning confocal microscopy, this study demonstrated that surface expression of the
 2 1 (VLA-2) integrin, though absent on
blood PMN, is induced in extravasated PMN collected from human skin
blister chambers, and rat PMN accumulated in the peritoneal cavity
after chemotactic stimulation. Intravital time-lapse videomicroscopy
was used to investigate chemoattractant-induced PMN locomotion in the
rat mesentery in vivo. Local administration of function-blocking
monoclonal antibody or peptide recognizing the
21 integrin reduced PMN migration
velocity in the extravascular tissue by 73% ± 3% and 70% ± 10%, respectively (means ± SD). The distance
f-met-leu-phe peptide (fMLP)-stimulated human PMN migrated in a
collagen gel in vitro was markedly reduced by treatment with
anti-2 mAbs or peptide, whereas no effect was observed
with antibodies or peptides recognizing the
41 or 51
integrins. Further evidence for a critical role of expression of
21 integrin in PMN locomotion in
extravascular tissue was obtained in the mouse air pouch model of acute
inflammation where chemoattractant-induced PMN recruitment was
substantially inhibited by local anti-2 mAb treatment.
Thus, expression of 21 integrin on
extravasated PMN has been identified and a novel role of this receptor
in regulating the extravascular phase of leukocyte trafficking in
inflammation has been formulated.
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