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Published online before print June 3, 2004

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(Journal of Leukocyte Biology. 2004;76:359-367.)
© 2004 by Society for Leukocyte Biology

Insulin cell mass is altered in Csf1^op/Csf1^op macrophage-deficient mice

Linda Banaei-Bouchareb^*,, Valerie Gouon-Evans, Dinane Samara-Boustani^*,, Marie Claire Castellotti^*, Paul Czernichow^*,¶, Jeffrey W. Pollard^|| and Michel Polak^*,,,1

^* INSERM U457 and
^¶ Paediatric Endocrinology Department, Robert Debré Teaching Hospital, Paris, France;
EMI0363 Necker University, Paris, France;
Mount Sinai School of Medicine, New York, NY;
Paediatric Endocrinology Department, Necker-Enfants-Malades Teaching Hospital, Paris, France; and
^|| Albert Einstein College of Medicine, Bronx, NY

¹Correspondence: Service d’Endocrinologie et Diabétologie Pédiatriques, Hôpital Necker Enfants-Malades, 149 rue de Sèvres, 75015 Paris, France. E-mail: michel.polak{at}nck.ap-hop-paris.fr

Macrophages play an important role in organ development, tissue homeostasis, and remodeling. 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 Csf1^op/Csf1^op (op/op) mice. The combined use of immunohistochemistry, morphometry, and cell quantification allows us to evaluate insulin and glucagon cell mass, total and insulin cell proliferation, and apoptosis in fetuses (E18.5), weanings (postnatal day 21), nonpregnant adults, and adults in late pregnancy (18.5 days). F4/80-positive macrophages were found in pancreases recovered from Csf1^op/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 major insulin mass deficit in fetuses and adults, abnormal 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 demonstration of the colony-stimulating factor 1-dependent macrophage involvement in life-time pancreas development/remodeling allows us to pinpoint the tissue-modeling and remodeling functions of this leukocyte lineage.

Key Words: pancreas • development • remodeling • pregnancy • osteopetrotic mice

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