Deficient collagen-induced activation in the newborn platelet.
We have investigated the impaired secretion response of neonatal platelets. We compared the response of washed neonatal and adult platelets to thrombin and collagen, and to specific activators of calcium flux (inositol trisphosphate) and protein kinase C activation (oleoyl-acetyl glycerol). Neonatal platelets show no impairment of aggregation, secretion of [14C]serotonin or phosphorylation of specific intracellular proteins in response to thrombin, inositol trisphosphate, or oleoyl-acetyl glycerol. However, neonatal platelets have a markedly decreased response to collagen. To further evaluate this deficient response, we examined specific aspects of the collagen activation pathway. Collagen-platelet interaction as measured by adhesion of platelets to collagen-coated dishes showed no difference in adhesion of neonatal platelets compared to adult controls (20.1 +/- 11.6 versus 18.6 +/- 9.3%). The presence of GPIa/IIa, a Mg2(+)-dependent collagen receptor, was evaluated by flow cytometric analysis of binding of fluorescein-tagged monoclonal antibody, 6F1 (directed against GPIa/IIa). There was no difference either in the percent of platelets that bound antibody (80 versus 81%) or in the mean fluorescence intensity of the adult and neonatal samples. Phosphoinositide hydrolysis was decreased in neonatal platelets in response to collagen but normal in response to thrombin. Neonatal platelets released more arachidonic acid than adult platelets in response to thrombin (29.5 +/- 3.2 versus 19.6 +/- 1.8%) but less than adult platelets in response to 10 micrograms/mL collagen (3.2 +/- 1.1 versus 9.3 +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
Israels
S J
SJ
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Daniels
M
M
McMillan
E M
EM
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn / Q000097:blood*; D007295:Inositol Phosphates / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D001798:Blood Proteins; D007295:Inositol Phosphates; D016718:Arachidonic Acid; D012701:Serotonin; D013929:Thromboxane B2; D003094:Collagen; D013917:Thrombin