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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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Submitted June 16, 2004
Accepted November 2, 2004
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*
Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy; Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, Guy's Campus, King's College, London, UK
Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
Pneumology Unit, Ospedale S. Maria, University of Perugia, Terni, Italy
Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, Guy's Campus, King's College, London, UK
* Corresponding author; email: grespa{at}unipg.it.
Platelets are necessary for lung leukocyte recruitment in a murine model of allergic inflammation, and platelet-leukocyte aggregates are formed in circulating blood of asthmatics 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 VLA-4 expression in mice.
Pulmonary leukocyte recruitment in platelet-depleted mice (sensitized and exposed to ovalbumin) transfused with fixed, unstimulated platelets (FUSP) was abolished, whereas transfusion with stimulated and fixed platelets (FSP), expressing P-selectin and PSGL-1, restored eosinophil and lymphocyte recruitment. Transfusion with platelets from P-selectin deficient mice, or with FSP 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 FSP, but not FUSP, a phenomenon concurrent with the formation of platelet-leukocyte complexes.
P-selectin expression on the surface 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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