title: Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice.
abstract: OBJECTIVE
  Although the cells that contribute to pancreatic regeneration have been widely studied, little is known about the mediators of this process. During tissue regeneration, infiltrating macrophages debride the site of injury and coordinate the repair response. We investigated the role of macrophages in pancreatic regeneration in mice.
  
  
  METHODS
  We used a saporin-conjugated antibody against CD11b to reduce the number of macrophages in mice following diphtheria toxin receptor-mediated cell ablation of pancreatic cells, and evaluated the effects on pancreatic regeneration. We analyzed expression patterns of infiltrating macrophages after cell-specific injury or from the pancreas of nonobese diabetic mice. We developed an in vitro culture system to study the ability of macrophages to induce cell-specific regeneration.
  
  
  RESULTS
  Depletion of macrophages impaired pancreatic regeneration. Macrophage polarization, as assessed by expression of tumor necrosis factor-α, interleukin 6, interleukin 10, and CD206, depended on the type of injury. The signals provided by polarized macrophages promoted lineage-specific generation of acinar or endocrine cells. Macrophage from nonobese diabetic mice failed to provide signals necessary for β-cell generation.
  
  
  CONCLUSIONS
  Macrophages produce cell type-specific signals required for pancreatic regeneration in mice. Additional study of these processes and signals might lead to new approaches for treating type 1 diabetes or pancreatitis.
authors.affiliation: Department of Surgery, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania.
authors.forename: Angela
authors.initials: A
authors.lastname: Criscimanna
authors.affiliation: Department of Surgery, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Coudriet
authors.affiliation: Department of Surgery, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania.
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
authors.affiliation: Department of Surgery, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
authors.affiliation: Department of Surgery, Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Electronic address: farzad.esni@chp.edu.
authors.forename: Farzad
authors.initials: F
authors.lastname: Esni
mesh_terms: D061354:Acinar Cells / Q000378:metabolism* / Q000473:pathology; D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004167:Diphtheria Toxin / Q000633:toxicity; D004195:Disease Models, Animal; D018796:Immunoconjugates / Q000633:toxicity; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010641:Phenotype; D012038:Regeneration; D054789:Ribosome Inactivating Proteins, Type 1 / Q000633:toxicity; D000076985:Saporins; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D015415:Biomarkers; D039481:CD11b Antigen; D004167:Diphtheria Toxin; D018796:Immunoconjugates; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
keywords: Diabetes; Macrophage Polarization; NOD; Pancreatitis; Tissue Damage