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Macrophage polarization induced by oxidized phospholipids
Author(s) -
Kadl Alexandra,
Leitinger Norbert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a17-b
Subject(s) - inflammation , chemistry , chemokine , macrophage polarization , macrophage , microbiology and biotechnology , m2 macrophage , phospholipid , ccl7 , ccl2 , immunology , biology , biochemistry , in vitro , membrane
Functional heterogeneity is a hallmark of cells of the mononuclear phagocyte system. Macrophages (MPs) have been ascribed both pro‐ and anti‐inflammatory properties as they orchestrate the initiation, but also the resolution phases of inflammation. This plasticity in the functional properties of MPs is determined by the immunological microenvironment. MPs activated by INFγ and/or microbial products display an M1‐phenotype, and trigger a type I inflammation and a Th1 response, as seen in acute inflammation. In contrast, M2‐MPs include various forms of alternatively activated MPs that promote a type II inflammation and a Th2 response, as seen in chronic inflammation and within tumours. However, it is not known how an oxidized phospholipid‐enriched microenvironment in an atherosclerotic lesion would affect MP polarisation. Here we show that oxidized 1‐palmitoyl‐2‐arachidonoyl‐sn‐3‐glycero‐phosphorylcholine (OxPAPC), a biologically active component of lipoproteins and cell membranes, activates and polarizes MPs towards a unique phenotype (Ox‐MP), different from the classical M1 and the alternative M2‐type. RT‐PCR and FACS analysis showed that Ox‐MP express M1 chemokines such as KC, MCP‐1/JE, MCP‐3/CCL7, and Mip2, but neither the M1‐cytokines IL12 and TNF, nor the M2 markers IL10 and arginase. Ox‐MP are characterized by high expression levels of heme oxygenase 1, and also VEGF. Ox‐MP exhibit increased survival, reduced migratory capability and facilitated lipoprotein uptake, when compared to M1 or M2. HO‐1 expressing Ox‐MP are present in atherosclerotic lesions and hence we conclude that an oxidized phospholipid‐enriched microenvironment polarizes and activates MPs to propagate chronic inflammation but also facilitate foam cell formation.