The effects of colony-stimulating factor-1 on the distribution of mononuclear phagocytes in the developing osteopetrotic mouse

Colony-stimulating factor-1 (CSF-1), the primary regulator of mononuclear phagocyte (M Phi) production, exists as either a circulating or cell surface, membrane-spanning molecule. To establish transplacental transfer of maternal CSF-1, gestational day-17 mothers were injected intravenously with I-125-mouse CSF-1 or human rCSF-1, and the I-125-cpm or human CSF-1 concentrations were measured in fetal tissue, placenta, and fetal/maternal sera. Biologically active CSF-1 crossed the placenta and peaked in fetal tissue, placenta, and serum 10 minutes after injection. The role of CSF-1 in perinatal M Phi, development was examined by studying the CSF-1-deficient osteopetrotic (csfm(op)/csfm(op)) mouse. Fetal/neonatal mice, derived from matings of either +/csfm(op) females with csfm(op)/csfm(op) males or the reciprocal pairings, were genotyped and tissue M Phi identified and quantified. In the presence of circulating maternal CSF-1 (+/csfm(op) mother), M Phi, development in csfm(op)/csfm(op) liver was essentially complete at birth relative to f/csfm(op) littermates, but significantly reduced in spleen, kidney, and lung. In the absence of circulating maternal CSF-1 (csfm(op)/csfm(op) mother), M Phi numbers at birth were reduced in csfm(op)/csfm(op) liver relative to the offspring of +/csfm(op) mothers, but were similar in spleen, kidney, and lung. We conclude that CSF-1 is required for the perinatal development of most M Phi, in these tissues. Compensation for total absence of local CSF-1 production by circulating, maternal CSF-1 is tissue-specific and most prominent in liver, the first fetal organ perfused by placental blood. However, because some M Phi developed in the complete absence of CSF-1, other factors must also be involved in the regulation of macrophage development. (C) 1998 by The American Society of Hematology.