Phosphocholine-containing Ligands Direct CRP Induction of M2 Macrophage Polarization Independent of T Cell Polarization: Implication for Chronic Inflammatory States

Overview

Journal Immun Inflamm Dis

Specialties Allergy & Immunology
Infectious Diseases

Date 2016 Sep 14

PMID 27621811

Citations 7

Authors

JoAnn Trial

Katarzyna A Cieslik

Mark L Entman

Affiliations

Soon will be listed here.

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 Fcγ 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 Fcγ receptors, which leads to macrophage activation independent of T cell signaling. We found that CRP plus PC acted via FcγRI, whereas CRP with liposomes bound to FcγRII. Both were activating signals as evidenced by SYK phosphorylation.

Conclusion: We conclude that CRP with ligands can promote M2 macrophage differentiation to fibroblasts through FcγR 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.

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