Platelets promote eosinophil adhesion of patients with asthma to endothelium under flow conditions.
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-alpha-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-selectin-bearing 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.
Ulfman
Laurien H
LH
Department of Pulmonar Diseases, University Medical Center, Utrecht, The Netherlands. L.Ulfman@hli.azu.nl
Joosten
Dianne P H
DP
van Aalst
Corneli W
CW
Lammers
Jan-Willem J
JW
van de Graaf
Ed A
EA
Koenderman
Leo
L
Zwaginga
Jaap Jan
JJ
D001249:Asthma / Q000097:blood* / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D010477:Perfusion / Q000379:methods; D012016:Reference Values; D014471:Umbilical Veins