Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation

TY - JOUR

T1 - Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation

AU - Pitchford, Simon C

AU - Momi, Stefania

AU - Giannini, Silvia

AU - Casali, Lucio

AU - Spina, Domenico

AU - Page, Clive P

AU - Gresele, Paolo

PY - 2005/3/1

Y1 - 2005/3/1

N2 - 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. (C) 2005 by The American Society of Hematology

AB - 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. (C) 2005 by The American Society of Hematology

KW - Animals

KW - Antigens, CD11b

KW - Blood Platelets

KW - Cell Adhesion

KW - Chemotaxis

KW - Disease Models, Animal

KW - Eosinophils

KW - Hypersensitivity

KW - Inflammation

KW - Integrin alpha4beta1

KW - Leukocytes

KW - Lung

KW - Lymphocytes

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - P-Selectin

U2 - 10.1182/blood-2004-06-2282

DO - 10.1182/blood-2004-06-2282

M3 - Article

C2 - 15528309

SN - 1528-0020

VL - 105

SP - 2074

EP - 2081

JO - Blood

JF - Blood

IS - 5

ER -