Apoptotic cells induce proliferation of peritoneal macrophages

  • 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.
Author:Anne-Kathrin Knuth, Arnaud HuardORCiDGND, Zumer NaeemGND, Peter RapplGND, Rebekka BauerORCiD, Ana Carolina Mota, Tobias SchmidORCiDGND, Ingrid FlemingORCiD, Bernhard BrüneORCiD, Simone FuldaORCiDGND, Andreas WeigertORCiDGND
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/02/24
Date of first Publication:2021/02/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/05/19
Tag:RNA sequencing; Zymosan-induced peritonitis; apoptosis; peritoneal macrophages; proliferation
Issue:5, art. 2230
Page Number:17
First Page:1
Last Page:17
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0