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 (Mphi) 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 Mphi development was examined by studying the CSF-1-deficient osteopetrotic (csfmop/csfmop) mouse. Fetal/neonatal mice, derived from matings of either +/csfmop females with csfmop/csfmop males or the reciprocal pairings, were genotyped and tissue Mphi identified and quantified. In the presence of circulating maternal CSF-1 (+/csfmop mother), Mphi development in csfmop/csfmop liver was essentially complete at birth relative to +/csfmop littermates, but significantly reduced in spleen, kidney, and lung. In the absence of circulating maternal CSF-1 (csfmop/csfmop mother), Mphi numbers at birth were reduced in csfmop/csfmop liver relative to the offspring of +/csfmop mothers, but were similar in spleen, kidney, and lung. We conclude that CSF-1 is required for the perinatal development of most Mphi 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 Mphi developed in the complete absence of CSF-1, other factors must also be involved in the regulation of macrophage development.
Roth
P
P
Division of Neonatology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
Dominguez
M G
MG
Stanley
E R
ER
D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005315:Fetal Diseases / Q000097:blood / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D010010:Osteoclasts / Q000473:pathology; D010022:Osteopetrosis / Q000097:blood / Q000196:embryology / Q000473:pathology*; D010586:Phagocytes / Q000187:drug effects*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy / Q000097:blood; D011994:Recombinant Proteins / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D013154:Spleen / Q000473:pathology
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor