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 (MΦ) 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 ¹²⁵I-mouse CSF-1 or human rCSF-1, end the ¹²⁵I-cpm or human CSF-1 concentrations were measured in fetal tissue, placenta, end fetal/maternal sere. Biologically active CSF-1 crossed the placenta end peaked in fetal tissue, placenta, and serum 10 minutes after injection. The role of CSF-1 in perinatal MΦ development was examined by studying the CSF- 1-deficient osteopatrotic (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 end tissue MΦ identified end quantified. In the presence of circulating maternal CSF-1 (+/csfm(op) mother), MΦ development in csfm(op)/csfm(op) liver was essentially complete at birth relative to +/csfm(op) littermates, but significantly reduced in spleen, kidney, and lung. In the absence of circulating maternal CSF-1 (csfm(op)/csfm(op) mother), MΦ 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 MΦ in these tissues. Compensation for total absence of local CSF-1 production by circulating, maternal CSF-1 is tissue-specific end most prominent in liver, the first fetal organ perfused by placental blood. However, because some MΦ developed in the complete absence of CSF-1, other factors must also be involved in the regulation of macrophage development.