Insulin cell mass is altered in Csf1op/Csf1op macrophage- deficient mice

Abstract: Macrophages play an important role in organ development, tissue homeostasis, and re-modeling. Thus, we monitored the presence of F4/ 80-positive macrophages in the pancreas of wild-type mice, and some developmental features of this complex tissue were compared throughout life in wild-type and macrophage-deficient Csf1op/Csf1op (op/op) mice. The combined use of immunohisto-chemistry, morphometry, and cell quantification allows us to evaluate insulin and glucagons cell mass, total and insulin cell proliferation, and apo-ptosis in fetuses (E18.5), weanings (postnatal day 21), nonpregnant adults, and adults in late preg-nancy (18.5 days). F4/80-positive macrophages were found in pancreases recovered from Csf1op/ Csf1 (op/) mice but were extremely scarce or absent in pancreas recovered from op/op ones at all studied time-points. The macrophage-deficient op/op phenotype was clearly associated with a ma-jor insulin mass deficit in fetuses and adults, abnor-mal postnatal islet morphogenesis, and impaired pancreatic cell proliferation at weaning and late pregnancy. We also obtained indirect evidence of increased neogenesis in this model at time-points when pancreatic remodeling does occur. The dem-onstration of the colony-stimulating factor 1-de-pendent macrophage involvement in life-time pan-creas development/remodeling allows us to pin-point the tissue-modeling and remodeling functions of this leukocyte lineage. J. Leukoc. Biol. 76