Characterization of static adhesion of human platelets in plasma to protein surfaces in microplates.
Platelet adhesion is a complex and important event for prevention of blood loss after vessel injury. This study investigated fundamental adhesive mechanisms occurring in an in-vitro assay developed for the measurement of static adhesion of human platelets in plasma. The aim was to gain methodological knowledge that could be used for interpretations of results from other studies using this specific assay. Involvement of adhesive receptors was investigated by the use of various antibodies as well as therapeutic drugs (abciximab, eptifibatide and tirofiban). Inhibitors of adenosine 5'-diphosphate receptors (cangrelor, MRS2179) and of thromboxane A(2) signalling (BM-531) were used to estimate the role of autocrine activation. Adhesion to collagen was found to be mainly mediated by alpha(2)beta(1) and to some extent by alpha(IIb)beta(3). Adhesion to fibrinogen was mediated by alpha(IIb)beta(3). In addition, adenosine 5'-diphosphate-induced adhesion to albumin was dependent on alpha(IIb)beta(3). Furthermore, experiments with cangrelor and BM-531 showed that the majority of the adhesive interactions tested were dependent on adenosine 5'-diphosphate or thromboxane A(2). We conclude that the mechanisms of adhesion measured by the static platelet adhesion assay are in accordance with the current knowledge regarding platelet activation and adhesion. Despite its simplicity, we suggest that this adhesion assay could be used as a screening device for the study of the influence of various surfaces and soluble substances on platelet adhesion.
Eriksson
Andreas C
AC
Division of Drug Research/Pharmacology, Department of Medical and Health Sciences, Linköping University, SE-581 83 Linköping, Sweden. andreas.eriksson@liu.se
Whiss
Per A
PA
D000077284:Abciximab; D000418:Albumins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D000077542:Eptifibatide; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010949:Plasma; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000418:Albumins; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D011506:Proteins; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014443:Tyrosine; D013928:Thromboxane A2; D005340:Fibrinogen; D003094:Collagen; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab