Uptake and Processing of Human Platelet Factor 4 by Hepatocytes

Abstract

Abstract

We previously demonstrated rapid clearance of human platelet factor 4 (PF4) from rabbit and rat blood, its accumulation in the liver, and elimination of PF4 degradation products in urine. The purpose of the present experiments was to characterize interaction of PF4 with cultured rat hepatocytes. ¹²⁵I-PF4 was taken up by hepatocytes reaching maximum at 180 min. The association of ¹²⁵I-PF4 with hepatocytes was two times greater at 37°C than at 4°C. At 37°C degradation of ¹²⁵I-PF4 by hepatocytes was also observed as indicated by the increase of ¹²⁵I-PF4 radioactivity soluble in 6% trichloroacetic acid. By contrast, no uptake of ¹²⁵I-β-throm-boglobulin antigen was observed. Autoradiography demonstrated that short incubation (5-20 min) of ¹²⁵I-PF4 with hepatocytes results in the association of ¹²⁵I-radioactivity with cell membranes while after longer incubation (60 min) radioactivity was also localized in the endosomes. Heparin inhibited binding and uptake of ¹²⁵I-PF4 radioactivity by hepatocytes. We propose that part of PF4 released in the circulating blood by activated platelets is bound to the surface of hepatocytes and that it is further processed by these cells.