Augmentation of superoxide generation in phagocytosing murine peritoneal macrophages by dietary restriction.

The effects of dietary restriction on the generation of superoxide anion (O2-) in phagocytosing mouse peritoneal macrophages (MPs) were investigated. MPs obtained from diet-restricted mice generated larger amount of O2- during phagocytosis of opsonized zymosan than those from unrestricted mice. This augmentation of the O2- generation was not inhibited by the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). However, the augmentation was clearly disappeared when the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was added. These results strongly suggest that the augmentation of O2- generation in phagocytosing MPs by dietary restriction is due to the increased activity of CaM in the MPs, and that PKC is not involved in the augmentation. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2- generation in MPs.