The pancreas anatomy conditions the origin and properties of resident macrophages.
We examine the features, origin, turnover, and gene expression of pancreatic macrophages under steady state. The data distinguish macrophages within distinct intrapancreatic microenvironments and suggest how macrophage phenotype is imprinted by the local milieu. Macrophages in islets of Langerhans and in the interacinar stroma are distinct in origin and phenotypic properties. In islets, macrophages are the only myeloid cells: they derive from definitive hematopoiesis, exchange to a minimum with blood cells, have a low level of self-replication, and depend on CSF-1. They express Il1b and Tnfa transcripts, indicating classical activation, M1, under steady state. The interacinar stroma contains two macrophage subsets. One is derived from primitive hematopoiesis, with no interchange by blood cells and alternative, M2, activation profile, whereas the second is derived from definitive hematopoiesis and exchanges with circulating myeloid cells but also shows an alternative activation profile. Complete replacement of islet and stromal macrophages by donor stem cells occurred after lethal irradiation with identical profiles as observed under steady state. The extraordinary plasticity of macrophages within the pancreatic organ and the distinct features imprinted by their anatomical localization sets the base for examining these cells in pathological conditions.
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Boris
B
Calderon
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Javier A
JA
Carrero
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Stephen T
ST
Ferris
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Dorothy K
DK
Sojka
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Lindsay
L
Moore
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Slava
S
Epelman
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110 Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Kenneth M
KM
Murphy
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110 Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110 Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Wayne M
WM
Yokoyama
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110.
Gwendalyn J
GJ
Randolph
Department of Pathology and Immunology; Division of Rheumatology and Division of Cardiology, Department of Medicine; and Howard Hughes Medical Institute; Washington University School of Medicine in St. Louis, St. Louis, MO 63110 unanue@wustl.edu.
Emil R
ER
Unanue
D000818:Animals; D000831:Animals, Newborn; D018845:CD11 Antigens / Q000235:genetics; D049109:Cell Proliferation; D004032:Diet; D020869:Gene Expression Profiling; D007515:Islets of Langerhans; D007962:Leukocytes / Q000166:cytology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010179:Pancreas / Q000033:anatomy & histology* / Q000166:cytology* / Q000196:embryology; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism
D018845:CD11 Antigens; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D016173:Macrophage Colony-Stimulating Factor