Penicillin-induced dysfunction of platelet membrane glycoproteins.
We examined the effects of the beta-lactam antibiotic penicillin G on platelet function and on specific membrane glycoproteins in vitro. Platelet concentrates exposed to 3 to 10 mmol/L penicillin for 48 hours showed irreversible inhibition of aggregation by thrombin in washed platelets after removal of the antibiotic. Although a brief 15-minute exposure to similar doses of penicillin also inhibited thrombin aggregation, the inhibition was reversed on removal of the penicillin by washing. Aggregation activity was also restored to normal levels by stimulation with high thrombin concentrations (> 0.4 U/ml). Results of the aggregation studies led us to examine how penicillin affects platelet membrane proteins. Membranes isolated after 48 hours of exposure of platelet concentrates to penicillin showed no differences from the control in total protein profiles on sodium dodecylsulfate--polyacrylamide gel electrophoresis or in the glycoprotein Ib or IIb content on immunoblotting. However, flow cytometric analysis with fluorescently labeled monoclonal antibodies revealed that exposure of platelets to penicillin for 15 minutes inhibited thrombin-induced modulations in the glycoproteins Ib, Ib-IX, IIb-IIIa, and P-selectin. These effects were observed with washed platelets and platelets in plasma. Penicillin also inhibited the regulation of expression of glycoproteins Ib-IX and IIb-IIIa in adenosine diphosphate--activated platelets. The inhibitory effects were partially reversed at high agonist concentrations.
Pastakia
K B
KB
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892.
Terle
D
D
Prodouz
K N
KN
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D010400:Penicillin G / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology
D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D013917:Thrombin; D010400:Penicillin G