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Secretory functions of macrophages in the human pancreatic islet are regulated by endogenous purinergic signaling
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posted on 2020-04-24, 19:54 authored by Ada AdminAda Admin, Jonathan R. Weitz, Carol Jacques-Silva, Mirza Muhammed Fahd Qadir, Oliver Umland, Elizabeth Pereira, Farhan Qureshi, Alejandro Tamayo, Juan Dominguez-Bendala, Rayner Rodriguez-Diaz, Joana Almaça, Alejandro CaicedoEndocrine cells of the
pancreatic islet interact with their microenvironment to maintain tissue
homeostasis. Communication with local macrophages is particularly important in
this context, but the homeostatic functions of human islet macrophages are not
known. Here we show that the human islet contains macrophages in perivascular
regions that are the main local source of the anti-inflammatory cytokine Il-10 and
the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic
factors is controlled by endogenous purinergic signals. In obese and diabetic
states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced.
We propose that in those states exacerbated beta cell activity due to increased
insulin demand and increased cell death produces high levels of ATP that
downregulate purinergic receptor expression. Loss of ATP sensing in macrophages
may reduce their secretory capacity.