Role of cytoplasmic and releasable ADP in platelet aggregation induced by laminar shear stress.
We examined the extent of lytic and sublytic platelet injury after exposure of platelets to shear stress and the role in shear-induced PAG of ADP liberated from platelets as a result of shear-induced platelet dense body release and/or platelet damage. Platelets in C-PRP or TAS were subjected to well-defined, laminar shear stress in a rotational viscometer, and PAG (loss of single, nonaggregated platelets), 14C-serotonin release, and loss from platelets of LDH and 51Cr were determined. Increased PAG with increasing shear stresses was associated with progressive loss of LDH and 51Cr. Loss of 51Cr was consistently in excess of that of LDH, indicating sublytic platelet injury, which was confirmed by electron microscopy. At the lowest shear stress used (50 dynes/cm2), PAG in C-PRP was observed in the absence of detectable loss of 51Cr or LDH. When platelets in TAS were sheared in the presence of CP/CPK, an enzyme system capable of removing extracellular ADP, PAG was only partially (approximately 40%) inhibited. However, when platelets were preincubated with CP/CPK and ATP (to saturate platelet ADP receptors), shear-induced PAG was almost completely suppressed. Similar results were obtained with PAG induced by collagen in the aggregometer. The findings indicate that (1) shear-induced PAG in this system may occur without measurable lytic or sublytic platelet damage and (2) ADP liberated from platelets as a result of shear-induced release or damage may represent the major if not sole mediator of shear-induced PAG.
D000244:Adenosine Diphosphate / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D002860:Chromium Radioisotopes / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000187:drug effects; D012399:Rotation; D012701:Serotonin / Q000378:metabolism; D013499:Surface Properties
D002860:Chromium Radioisotopes; D012701:Serotonin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase