Expression of P-selectin at low site density promotes selective attachment of eosinophils over neutrophils.
The selective interaction of neutrophils with E-selectin and eosinophils with P-selectin has been previously reported, but the relevance of selectin site density and fluid shear has not been studied in detail. We have developed a new approach to examine these interactions in cell suspensions that integrates an on-line cone-plate viscometer with a flow cytometer. We find that eosinophils and neutrophils both use P-selectin glycoprotein ligand-1 to form stable conjugates with P-selectin Chinese hamster ovary cell transfectants, with a preferential adhesion of eosinophils. Further, the difference in cell adhesion between neutrophils and eosinophils is magnified at P-selectin expression levels below approximately 20 sites/microm2, a range likely to be relevant to endothelial cell expression levels in conditions associated with eosinophilia. The unique behavior is retained over shear rates ranging from 100 to 1500/s but is magnified at low shear. Results from parallel-plate flow chamber assays suggest that preferential eosinophil adhesion reflects an enhanced efficiency of initial PSGL-1 bond formation with P-selectin rather than a unique ability of eosinophils to mediate rolling interactions of longer duration on low-density P-selectin substrates. These differences may account in part for the increase in eosinophil accumulation in allergic diseases.
Edwards
B S
BS
Department of Pathology and Cytometry, Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. Bedwards@salud.unm.edu
Curry
M S
MS
Tsuji
H
H
Brown
D
D
Larson
R S
RS
Sklar
L A
LA
D000818:Animals; D001666:Binding Sites, Antibody / Q000235:genetics; D001783:Blood Flow Velocity / Q000276:immunology; D016466:CHO Cells; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D006224:Cricetinae; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012044:Regression Analysis; D014162:Transfection
D019007:P-Selectin