Molecular determinants of aspirin-induced neutrophil adherence to endothelial cells.
BACKGROUND
Previous studies indicate that aspirin can promote neutrophil adhesion to venular endothelium in vivo. The objectives of the present study were (1) to identify the leukocyte and endothelial cell surface glycoproteins that mediate this adhesive interaction and (2) to assess the role of lipoxygenase products, prostanoids, and platelet activating factor in aspirin-induced neutrophil adhesion.


METHODS
Human neutrophils (polymorphonuclear leukocytes [PMN]) were added to confluent monolayers of human umbilical vein endothelial cells (HUVEC) and coincubated with or without aspirin (30, 150, or 300 micrograms/mL).


RESULTS
Aspirin increased neutrophil adherence to HUVEC in a dose-dependent manner. Pretreatment of HUVEC with aspirin had no effect on PMN adherence whereas pretreatment of PMN significantly increased adherence to HUVEC. Incubation of neutrophils with aspirin increased surface expression of CD11b and CD18 on neutrophils. The aspirin-induced increase in PMN adherence to HUVEC was significantly reduced by monoclonal antibodies against CD18, CD11b, CD11a, and intercellular adhesion molecule 1. Aspirin-induced neutrophil adhesion was diminished by treatment with either a lipoxygenase inhibitor or a leukotriene B4 (LTB4) receptor antagonist.


CONCLUSIONS
These studies indicate that aspirin promotes neutrophil adherence to endothelium via CD11a/CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule 1; the adhesion response is partially mediated by leukotriene B4.
Yoshida
N
N
Department of Physiology, Louisiana State University Medical Center, Shreveport.
Takemura
T
T
Granger
D N
DN
Anderson
D C
DC
Wolf
R E
RE
McIntire
L V
LV
Kvietys
P R
PR
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D001241:Aspirin / Q000494:pharmacology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4 / Q000378:metabolism / Q000502:physiology; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D010972:Platelet Activating Factor / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D010972:Platelet Activating Factor; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D001241:Aspirin