TY - JOUR
T1 - The pancreas anatomy conditions the origin and properties of resident macrophages
AU - Calderon, Boris
AU - Carrero, Javier A.
AU - Ferris, Stephen T.
AU - Sojka, Dorothy K.
AU - Moore, Lindsay
AU - Epelman, Slava
AU - Murphy, Kenneth M.
AU - Yokoyama, Wayne M.
AU - Randolph, Gwendalyn J.
AU - Unanue, Emil R.
N1 - Publisher Copyright:
© 2015 Tang et al.
PY - 2015/9/21
Y1 - 2015/9/21
N2 - 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 selfreplication, 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.
AB - 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 selfreplication, 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.
UR - http://www.scopus.com/inward/record.url?scp=84943384367&partnerID=8YFLogxK
U2 - 10.1084/jem.20150496
DO - 10.1084/jem.20150496
M3 - Article
C2 - 26347472
AN - SCOPUS:84943384367
SN - 0022-1007
VL - 212
SP - 1497
EP - 1512
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -