Inhibition of platelet receptors involved in neutrophil-platelet interaction in model cardiopulmonary bypass.
We investigated the interactions between neutrophils, platelets, and artificial surfaces, and whether blocking of relevant receptors on platelets reduced unwanted activation responses in model cardiopulmonary bypass. Isolated neutrophils and platelets resuspended in heparin-anticoagulated plasma were recirculated with and without blocking antibodies to CD62P, CD42b, or junctional adhesion molecule C (JAM-C) in polyvinyl chloride tubing using a roller pump. Platelet adhesion to the tubing was inhibited by anti-CD42b and anti-CD62P, and adhesion of neutrophils by anti-JAM-C. Formation of platelet-neutrophil and platelet aggregates was reduced by anti-CD62P. Anti-JAM-C decreased platelet-neutrophil aggregation at low concentrations and platelet macroaggregates at high concentrations. Anti-CD62P increased neutrophil CD11b expression but not degranulation. Anti-JAM-C substantially increased neutrophil degranulation and slightly increased CD11b expression. Platelet activation increased when CD62P was blocked and decreased with anti-CD42b antibody. High-dose anti-JAM-C reduced platelet activation. In conclusion, inhibiting platelet and neutrophil-platelet interactions had useful effects but no single blocking antibody seemed capable of inducing only beneficial effects.
Asberg
Ann Elisabeth
AE
Department of Immunology and Transfusion Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. ann.asberg@ntnu.no
Videm
Vibeke
V
D002315:Cardiopulmonary Bypass; D015815:Cell Adhesion Molecules; D005434:Flow Cytometry; D006801:Humans; D018375:Neutrophil Activation / Q000502:physiology*; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*
D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex