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

Abstract: Gene-targeted mice lacking the hemo-poietic growth factors, granulocyte colony-stimulat-ing factor (G-CSF) or granulocyte-macrophage (GM)-CSF, show increased susceptibility to infec-tion with the facultative intracellular bacterium, Listeria monocytogenes. The resident peritoneal cell populations from G-CSF2/2 and GM2CSF2/2 mice showed reduced production of the bacteri-cidal molecule nitric oxide. Macrophage-mediated tumoricidal activity and phagocytosis of Listeria were reduced in G-CSF2/2, but not in GM-CSF2/2, mice. In G-CSF2/2 mice, there was an unexpected expansion (from 18 % in WT to 38%) of a popula-tion of cells with morphology intermediate between typical macrophages and typical lymphocytes. These cells had some of the features of poorly differenti-ated 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 typi-cal macrophages, possibly accounts for some of the functional deficiencies observed in G-CSF2/2 mice