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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2074-2081.
Prepublished online as a Blood First Edition Paper on November 4, 2004; DOI 10.1182/blood-2004-06-2282.
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IMMUNOBIOLOGY
Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation
Simon C. Pitchford,
Stefania Momi,
Silvia Giannini,
Lucio Casali,
Domenico Spina,
Clive P. Page, and
Paolo Gresele
From the Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Italy; the Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, King's College London, United Kingdom; and the Pneumology Unit, University of Perugia, Terni, Italy.
Platelets are necessary for lung leukocyte recruitment in a murine model of allergic inflammation, and platelet–leukocyte aggregates are formed in circulating blood of patients with asthma after allergen exposure. However, it is unknown how platelets induce pulmonary leukocyte recruitment in asthma. Here, we have investigated the importance of platelet adhesion molecule expression on pulmonary eosinophil and lymphocyte recruitment and on leukocyte CD11b and very late antigen (VLA)–4 expression in mice. Pulmonary leukocyte recruitment in platelet-depleted mice (sensitized and exposed to ovalbumin) transfused with fixed, unstimulated platelets (FUSPs) was abolished, whereas transfusion with platelets stimulated and fixed (FSPs), expressing P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), restored eosinophil and lymphocyte recruitment. Transfusion with platelets from P-selectin–deficient mice, or with FSPs stimulated in the presence of a blocking anti–P-selectin antibody, were unable to restore pulmonary leukocyte recruitment. Flow cytometric analysis revealed increased expression of CD11b and VLA-4 on leukocytes attached to platelets after allergen exposure, and CD11b expression on leukocytes was suppressed in thrombocytopenic mice but was restored with the transfusion of FSPs, but not FUSPs, a phenomenon concurrent with the formation of platelet–leukocyte complexes. P-selectin expression on the surfaces of platelets is a major requirement for pulmonary eosinophil and lymphocyte recruitment, allowing circulating platelets to bind to and stimulate leukocytes for endothelial attachment.
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