Decreased intraplatelet Ca2+ release and ATP secretion in pediatric nephrotic syndrome.
Platelets play an important role in the natural history of idiopathic nephrotic syndrome (NS). Although thromboembolic events are rare, the activation of circulating platelets is generally considered an important factor in the prethrombotic state in children with NS. Platelet-activating factor (PAF), a potent endogenous phospholipid mediator of inflammation, stimulates intracellular free calcium (Ca2+) mobilization, aggregation, and release reactions in platelets obtained from normal donors. Platelet-related effects of PAF in children with NS are unknown. We studied PAF-induced intracellular Ca2+ mobilization in washed platelets and ATP secretion in platelet-rich plasma in 34 children with idiopathic NS and in 7 healthy children. There was a significant decrease in ATP secretion: 0.021+/-0.011 microg/10(7) cells with 20 nM PAF and 0.089+/-0.017 microg/10(7) platelets with 200 nM PAF versus control values (0.195+/-0.004 microg/10(7) and 0.813+/-0.09 microg/10(7), respectively). Moreover, PAF-evoked increase in intracellular free Ca2+ concentration was twofold lower in NS patients than in control subjects (230.1+/-22.4 nM versus 455.6+/-15.3 nM). Also, thrombin-induced intracellular free Ca2+ mobilization was diminished in children with NS compared with the control group. Thus, contrary to expectations, a decrease of platelet reactivity in response to PAF in vitro was observed in children with idiopathic NS. We suggest that this decreased platelet reactivity may reflect a period refractory to PAF and may be considered as platelet desensitization to PAF released in vivo in children with NS.
Svetlov
S I
SI
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. stanislav.svetlov@yale.edu
Moskaleva
E S
ES
Pinelis
V G
VG
Daikhin
Y
Y
Serebruany
V L
VL
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000293:Adolescent; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D010972:Platelet Activating Factor; D000255:Adenosine Triphosphate; D013917:Thrombin; D002118:Calcium