TY - JOUR A1 - Knuth, Anne-Kathrin A1 - Huard, Arnaud A1 - Naeem, Zumer A1 - Rappl, Peter A1 - Bauer, Rebekka A1 - Mota, Ana Carolina A1 - Schmid, Tobias A1 - Fleming, Ingrid A1 - BrĂ¼ne, Bernhard A1 - Fulda, Simone A1 - Weigert, Andreas T1 - Apoptotic cells induce proliferation of peritoneal macrophages T2 - International journal of molecular sciences N2 - The interaction of macrophages with apoptotic cells is required for efficient resolution of inflammation. While apoptotic cell removal prevents inflammation due to secondary necrosis, it also alters the macrophage phenotype to hinder further inflammatory reactions. The interaction between apoptotic cells and macrophages is often studied by chemical or biological induction of apoptosis, which may introduce artifacts by affecting the macrophages as well and/or triggering unrelated signaling pathways. Here, we set up a pure cell death system in which NIH 3T3 cells expressing dimerizable Caspase-8 were co-cultured with peritoneal macrophages in a transwell system. Phenotype changes in macrophages induced by apoptotic cells were evaluated by RNA sequencing, which revealed an unexpectedly dominant impact on macrophage proliferation. This was confirmed in functional assays with primary peritoneal macrophages and IC-21 macrophages. Moreover, inhibition of apoptosis during Zymosan-induced peritonitis in mice decreased mRNA levels of cell cycle mediators in peritoneal macrophages. Proliferation of macrophages in response to apoptotic cells may be important to increase macrophage numbers in order to allow efficient clearance and resolution of inflammation. KW - apoptosis KW - peritoneal macrophages KW - RNA sequencing KW - Zymosan-induced peritonitis KW - proliferation Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/60993 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-609937 SN - 1422-0067 VL - 22 IS - 5, art. 2230 SP - 1 EP - 17 PB - Molecular Diversity Preservation International CY - Basel ER -