Phosphocholine-containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states.

ABSTRACT:

Introduction

We studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C-reactive protein (CRP) with two disease-related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids.

Methods

We used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fc? receptors in monocytes.

Results

CRP without ligands did not promote M2 macrophage differentiation over background levels. However, when paired with either ligand, it increased M2 numbers. M2 differentiation was dependent on IL-13, and in the case of CRP with PC, was associated with a Th2 response. Paradoxically, while CRP with PC initiated a Th2 response, the combination of liposomes with CRP resulted in a Th1 response without any change in Th2 numbers despite association with M2 macrophage polarization. To resolve the conundrum of an anti-inflammatory macrophage response coexisting with a proinflammatory T cell response, we investigated signaling of CRP and its ligands through Fc? receptors, which leads to macrophage activation independent of T cell signaling. We found that CRP plus PC acted via Fc?RI, whereas CRP with liposomes bound to Fc?RII. Both were activating signals as evidenced by SYK phosphorylation.

Conclusion

We conclude that CRP with ligands can promote M2 macrophage differentiation to fibroblasts through Fc?R activation, and this may result in an anti-inflammatory influence despite a proinflammatory T cell environment caused by oxidized lipids. The potential relationship of this mechanism to chronic inflammatory disease is discussed.

SUBMITTER: Trial J 

PROVIDER: S-EPMC5004283 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature