Effects of essential fatty acid deficiency and indomethacin on histologic, ultrastructural, and phagocytic responses of hepatic macrophages to glucan.
Glucan administration in the rat induces a hyperplasia and hypertrophy of the reticuloendothelial system (RES) and a concomitant leukocytosis. Increased phagocytic function and lysozymal immunoreactivity of macrophages are also characteristic of the glucan effect. The potential role of arachidonic acid metabolites in mediating this hepatic inflammatory response induced by the RES stimulant glucan was assessed in the present study by two experimental approaches. In one study, rats were depleted of arachidonic acid by rendering them deficient in essential fatty acids (EFA). In another study, rats were pretreated with the fatty acid cyclooxygenase inhibitor indomethacin. Both treatment interventions markedly attenuated the hepatic Kupffer cell proliferative and granulomatous response to glucan and the associated leukocytosis. Lysozyme immunoreactivity of the Kupffer cells and rates of colloidal carbon clearance (T/2), however, were enhanced by the above treatments. Supplementation of EFA-deficient rats with ethyl arachidonate restored their glucan response to an extent that was not significantly different from nondeficient rats. Marked hepatic proliferative responses were apparent only in those treatment groups characterized by leukocytosis, which suggests that extrahepatic recruitment is an important component of the glucan response in normal, nutritionally adequate rats. Collectively these data suggest that arachidonic acid metabolites may play a role in modulating this extrahepatic recruitment and the associated cellular proliferative and granulomatous responses following glucan administration of the rat.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005936:Glucans / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007728:Kupffer Cells / Q000201:enzymology / Q000648:ultrastructure; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D009113:Muramidase / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D005228:Fatty Acids, Essential; D005936:Glucans; D016718:Arachidonic Acid; D009113:Muramidase; D007213:Indomethacin