Distinct in vivo functions of two macrophage subpopulations as evidenced by studies using macrophage-deficient op/op...

The op/op mice totally lack macrophage growth factor colony-stimulating factor (CSF)-1 and thus, by definition are completely depleted of CSF-1-dependent functions of the macrophage cell lineage. Moreover, they possess a severe and generalized macrophage deficiency. However, residual macrophages of these mice should still have normal CSF-1-independent functions. Studies designed to elucidate this issue have revealed that op/op mice are capable of normal in vivo phagocytic function and demonstrate normal humoral and cellular response postimmunization with sheep red blood cells. However, release of monokines such as tumor necrosis factor and granulocyte CSF following administration of endotoxin is severely impaired in op/op mice as compared with littermate controls. These studies suggest that the CSF-1-dependent macrophage population (absent in the op/op mouse) is primarily responsible for regulatory functions of these cells mediated by monokines, while the CSF-1-independent macrophage population (present in the op/op mouse) is primarily responsible for the classical macrophage functions in immunity such as phagocytosis, antigen processing and presentation.