EFFECTS OF SODIUM PERIODATE ON PLATELET FUNCTIONS

Abstract

NaIO4 (1 to 10 mM) caused aggregation of stirred suspensions of washed platelets from rabbits. Ca was required in the suspending medium for NaIO4-induced aggregation. Aggregation was not accompanied by the release of amine storage granule contents nor by cell lysis. Aggregation induced by NaIO4 was not inhibited by creatine phosphate-creatine phosphokinase, by platelet inhibitors that raised platelet cyclic AMP levels such as prostaglandin E1 or methylxanthines, by agents that modify platelet surface sulfhydryl groups (N-ethylmaleimide, p-chloromercuribenzene sulfonate), nor by cytochalasin B and/or colchicine which interfered with platelet contractile processes. Drugs such as acetylsalicylic acid, penicillin G, or cephalothin had no effect on NaIO4-induced aggregation. NaIO4-induced aggregation was practically independent of platelet metabolism since it was not affected by low temperatures and was only slightly inhibited by a combination of antimycin and iodoacetate. Periodate treatment enhanced CO2 production by platelets. When rabbit platelets were pretreated, without stirring, with NaIO4 (0.01 to 1 mM), they did not aggregate. They retained their disc shape and granule contents. This pretreatment with NaIO4 inhibited aggregation induced by ADP and inhibited both aggregation and release induced by collagen, thrombin, arachidonic acid and the ionophore A23,187. The extent of inhibition corresponded to the concentration of NaIO4 used to pretreat the platelets. In contrast, concanavalin A-induced aggregation was unchanged by NaIO4 pretreatment. When NaIO4 oxidation was followed by sodium borohydride (NaBH4) reduction, the effects caused by NaIO4 pretreatment on ADP-induced aggregation and collagen- or thrombin-induced aggregation and release were partially reversed. Pretreatment with NaIO4 also diminished the rate of serotonin uptake and decreased the ability of platelets to adhere to collagen-coated surfaces or to the subendothelial structures of the rabbit aorta. Platelets which had been treated with NaIO4 and then reinfused into rabbits did not survive, and in this way were similar to platelets from which surface sialic acid was removed by neuraminidase treatment. Since NaIO4 is known to oxidize sialic acid on red cell membranes, it seems probable that alteration of surface sialic acid resulted in recognition of the periodate-treated platelets as foreign by the RES. When NaIO4 oxidation was followed by NaBH4 reduction, platelet survival returned toward normal values.