title: Platelet-activating factor in plasma of patients with sickle cell disease in steady state.
abstract: The role of platelet-activating factor (PAF) in the pathogenesis of microvascular vaso-occlusion in sickle cell disease (SCD) is not known. In order to assess a role for PAF in vaso-occlusion in patients with SCD in steady state conditions, we measured plasma PAF level and plasma PAF acetylhydrolase activity as indices of PAF metabolism in vivo. We also studied PAF synthesis, from (3H)-acetate, by purified platelets stimulated with A23187. PAF was extracted from plasma of ten patients with SCD in steady state and from age-matched controls. PAF, purified by thin-layer chromatography, was quantitated by radioimmunoassay. PAF level (mean +/- SEM, pg/ml) in plasma of controls was 393 +/- 65, which was significantly lower than the 797 +/- 62 measured in plasma of patients with SCD. There was no difference in acetylhydrolase activity between the two groups. PAF synthesis (mean +/- SEM, nmol/10(6) cells) by platelets of controls without exogenous lyso-PAF was 1.69 +/- 0.24, higher than the 0.59 +/- 0.038 synthesized by platelets of patients with SCD. Incubation of platelets with 1.0 micromol/L lyso-PAF increased PAF synthesis by controls to 8.93 +/- 1.76, still higher than the 4.59 +/- 0.98 synthesized by platelets of patients with SCD. Our data show that patients with SCD are susceptible to a higher circulating levels of PAF in vivo during steady-state conditions. We speculate that higher levels of PAF may be a contributing factor to the persistent stress and inflammatory state of the microcirculation of patients with SCD.
authors.affiliation: Department of Pediatrics, University of California at Los Angeles School of Medicine, Torrance, USA.
authors.forename: S O
authors.initials: SO
authors.lastname: Oh
authors.forename: B O
authors.initials: BO
authors.lastname: Ibe
authors.forename: C
authors.initials: C
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Kurantsin-Mills
authors.forename: J U
authors.initials: JU
authors.lastname: Raj
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000293:Adolescent; D000328:Adult; D000375:Aging; D000755:Anemia, Sickle Cell / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D001835:Body Weight; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D010741:Phospholipases A / Q000097:blood; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D010976:Platelet Count
chemical_list: D006454:Hemoglobins; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase