American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 512-519, 2003
© 2003 American Thoracic Society DOI: 10.1165/rcmb.4806
Platelets Promote Eosinophil Adhesion of Patients with Asthma to Endothelium under Flow Conditions
Laurien H. Ulfman,
Dianne P. H. Joosten,
Corneli W. van Aalst,
Jan-Willem J. Lammers,
Ed A. van de Graaf,
Leo Koenderman and
Jaap Jan Zwaginga
Department of Pulmonary Diseases, University Medical Center, Utrecht; and Central Laboratory for Blood Transfusion, Amsterdam, The Netherlands
Address correspondence to: Laurien H. Ulfman, Heidelberglaan 100 hpn G03 550, 3584 CX, Utrecht, The Netherlands. E-mail: L.Ulfman{at}hli.azu.nl
During the late-phase asthmatic response, eosinophils migrate to the bronchial tissue and cause severe damage. In this study we compared in vivo primed eosinophils from patients with allergic asthma with eosinophils from healthy control subjects in their adhesion behavior to tumor necrosis factor- activated endothelium under flow conditions (0.8 dyn/cm2). More eosinophils from patients with asthma adhered to activated endothelium, compared with cells from healthy control subjects (1,237 ± 126 versus 887 ± 94 cells/mm2, respectively). In the presence of blocking antibodies directed against very late antigen-4 and E-selectin, the residual binding of the cells of individuals with allergic asthma was significantly higher than that of the healthy control subjects (353 ± 64 versus 123 ± 31 cells/mm2, respectively, P < 0.02). In addition, secondary tethering or formation of clusters of the eosinophils of patients with allergic asthma was significantly increased compared with the healthy control subjects (cluster indices 1.8 ± 0.3 versus 0.8 ± 0.2, respectively, P < 0.05). Because patient cells showed an enhanced interaction with platelets during the perfusions, the role of P-selectin on platelets was investigated. Blocking antibodies directed against P-selectin reduced the enhanced binding and clustering of eosinophils of patients with allergic asthma. We conclude that P-selectinbearing platelets contribute to secondary tethering processes of eosinophils to activated endothelium. Therefore, platelets might play an important role in the chronic inflammatory processes of these patients.
Abbreviations: fluorescence-activated cell sorter, FACS human serum albumin, HSA human umbilical vein endothelial cell, HUVEC intercellular adhesion molecule, ICAM interleukin, IL platelet-activating factor, PAF tumor necrosis factor- , TNF- vascular cell adhesion molecule, VCAM very late antigen, VLA
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Copyright © 2003 American Thoracic Society.
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