Human peritoneal macrophages show functional characteristics of M-CSF-driven anti-inflammatory type 2 macrophages

Abstract

We have recently shown that in vitro polarized M-CSF-driven anti-inflammatory macrophages (MPhi2) have the unique capacity to preferentially bind and ingest early apoptotic cells. However, these data are based on in vitro polarized cells and it is unclear whether MPhi2-like cells exist in vivo. Here we used CD163 as a cell surface marker to distinguish MPhi2 from the pro-inflammatory MPhi1. We show that human peritoneal MPhi (pMPhi) freshly isolated from patients on peritoneal dialysis have the phenotypical characteristics of MPhi2, including CD163 surface expression and lack of CD16. Like MPhi2, pMPhi have the capacity for endocytosis and macropinocytosis, are able to preferentially bind and ingest early apoptotic cells, and produce large amounts of IL-10 upon stimulation with LPS. Moreover, upon LPS stimulation both pMPhi and MPhi2 down-regulate CD86, resulting in a reduced capacity to stimulate proliferation of allogeneic T cells and an inhibition of Th1 cytokine release of these T cells. Our data provide the evidence for the first time that in vitro polarized MPhi2 exist in vivo, and human pMPhi resemble the anti-inflammatory MPhi2. We propose that pMPhi have the potential to maintain an anti-inflammatory condition in the peritoneal cavity.