607 DEFECTIVE MICROTUBULE RELATED FUNCTIONS OF PHAGOCYTES IN GLUTATHIONE PEROXIDASE DEFICIENT RATS

Abstract

Peritoneal polymorphonuclear leukocytes (PMN) obtained from rats rendered glutathione peroxidase (GPX) deficient after an eight week selenium deficient diet exhibited defective chemotaxis and degranulation and enhanced spontaneous surface glycoprotein capping. To compare the phagocytic function of peritoneal macrophages (PM) to PMN, cells were obtained from the peritoneal cavity of rats and purified on a Ficoll-hypaque gradient. PMN and PM GPX activity after 10 weeks of diet was 7% and 15% of control respectively. Similar to the PMN, the PM exhibited negligible chemotaxis, elevated spontaneous capping of 28.6 ± 6.3% compared to 12.8 ± 1% for controls and impaired intracellular killing of StaphyTococcus aureus 502A. Unlike the PMN, regurgitation of the lysosomal enzyme Beta-glucuronidase during phagocytosis was normal. The proportion of cytoplasmic depolymerized microtubules as determined by a radioactive colchicine binding assay was increased during phagocytosis in the GPX deficient PMN rather than decreased as observed in control. These studies show that rat PM rendered GPX deficient share certain functional abnormalities dependent upon intact microtubules but unlike PMN, degranulation appears less dependent on microtubules. Furthermore, in the GPX deficient PMN, microtubules appear to be susceptible to peroxidative damage during phagocytosis.