The Effects of Colony-Stimulating Factor-1 on the Distribution of Mononuclear Phagocytes in the Developing Osteopetrotic Mouse

Abstract

Colony-stimulating factor-1 (CSF-1), the primary regulator of mononuclear phagocyte (M▹) 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, and the 125I-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▹ development was examined by studying the CSF-1–deficient osteopetrotic (csfmop/csfmop) mouse. Fetal/neonatal mice, derived from matings of either +/csfmopfemales with csfmop/csfmop males or the reciprocal pairings, were genotyped and tissue M▹ identified and quantified. In the presence of circulating maternal CSF-1 (+/csfmop mother), M▹ development incsfmop/csfmop liver was essentially complete at birth relative to +/csfmoplittermates, but significantly reduced in spleen, kidney, and lung. In the absence of circulating maternal CSF-1 (csfmop/csfmop mother), M▹ numbers at birth were reduced in csfmop/csfmopliver relative to the offspring of +/csfmopmothers, but were similar in spleen, kidney, and lung. We conclude that CSF-1 is required for the perinatal development of most M▹ 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▹ developed in the complete absence of CSF-1, other factors must also be involved in the regulation of macrophage development.