Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF or GM-CSF

Abstract

Gene-targeted mice lacking the hemopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage (GM)-CSF, show increased susceptibility to infection with the facultative intracellular bacterium, Listeria monocytogenes. The resident peritoneal cell populations from G-CSF(-/-) and GM-CSF(-/-) mice showed reduced production of the bactericidal molecule nitric oxide. Macrophage-mediated tumoricidal activity and phagocytosis of Listeria were reduced in G-CSF(-/-), but not in GM-CSF(- /-), mice. In G-CSF(-/-) mice, there was an unexpected expansion (from 18% in WT to 38%) of a population of cells with morphology intermediate between typical macrophages and typical lymphocytes. These cells had some of the features of poorly differentiated macrophages, being adherent to plastic but poorly phagocytic, nonspecific esterase positive but myeloperoxidase negative. They were largely negative for the macrophage marker F4/80 and for Thy1, B220, and Gr1. Their disproportionate presence, and the corresponding deficiency in typical macrophages, possibly accounts for some of the functional deficiencies observed in G-CSF(-/-) mice.