Limits...
Innate immunity and monocyte-macrophage activation in atherosclerosis.

Shalhoub J, Falck-Hansen MA, Davies AH, Monaco C - J Inflamm (Lond) (2011)

Bottom Line: Innate inflammation is a hallmark of both experimental and human atherosclerosis.The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets.Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytokine Biology of Atherosclerosis, Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, UK. c.monaco@imperial.ac.uk.

ABSTRACT
Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

No MeSH data available.


Related in: MedlinePlus

Macrophages have classically been described as M1 and M2. These two phenotypes differ substantially with respect to the expression of macrophage associated genes. More recently, Kadl et al have described a new subset termed MOX macrophages [36]. These are induced by an environment rich in structurally defined oxidation products such as oxidised 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC) and can be induced from an M1 or M2 phenotype. ARE, antioxidant responsive elements; ARG1, arginase 1; CCL, chemokine ligand; COX2, cyclo-oxygenase 2; CXCL, chemokine CXC motif ligand; FIZZ1, found in inflammatory zone 1; GR, galactose receptor; HO1, heme-oxygenase 1; IL, interleukin; IL1ra; interleukin 1 receptor antagonist; ILR2, interleukin 1 receptor type II, decoy receptor; iNOS, inducible nitric oxide synthase; NRF2, nuclear factor erythroid 2-like 2; SR, scavenger receptor; Ym1, chitinase 3-like 3 lectin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3094203&req=5

Figure 1: Macrophages have classically been described as M1 and M2. These two phenotypes differ substantially with respect to the expression of macrophage associated genes. More recently, Kadl et al have described a new subset termed MOX macrophages [36]. These are induced by an environment rich in structurally defined oxidation products such as oxidised 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC) and can be induced from an M1 or M2 phenotype. ARE, antioxidant responsive elements; ARG1, arginase 1; CCL, chemokine ligand; COX2, cyclo-oxygenase 2; CXCL, chemokine CXC motif ligand; FIZZ1, found in inflammatory zone 1; GR, galactose receptor; HO1, heme-oxygenase 1; IL, interleukin; IL1ra; interleukin 1 receptor antagonist; ILR2, interleukin 1 receptor type II, decoy receptor; iNOS, inducible nitric oxide synthase; NRF2, nuclear factor erythroid 2-like 2; SR, scavenger receptor; Ym1, chitinase 3-like 3 lectin.

Mentions: Macrophage phenotypic polarisation may have a role in the fate of an atherosclerotic plaque. The plaque is an environment with a strong skew towards Th1 lymphocytic responses, resulting in high levels of IFNγ [33,34] which could in theory privilege M1-type macrophage polarisation. However, studies thus far have demonstrated macrophage heterogeneity within atherosclerosis, supporting that both M1 and M2 macrophages are present in human and murine atherosclerotic lesions. In an ApoE-/- murine model of atherosclerosis, early lesions were seen to be infiltrated by M2 (arginase I+) macrophages [35]. As lesions progressed a phenotypic switch was observed, with an eventual predominance of M1 (arginase II+) macrophages. Upon exposure to the oxidised phospholipid 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC), murine macrophages adopted a previously undescribed phenotype (Figure 1) [36]. A reduction in the expression of genes characteristic of both M1 and M2, coupled with an up-regulation of a unique redox gene signature that includes haemoxygenase 1, was observed. This population, termed Mox macrophages, are nuclear factor erythroid 2-like 2 (Nrf2)-dependent and have been shown to comprise approximately 30% of all macrophages in advanced atherosclerotic lesions of LDLR-/- mice [36]. A variety of subtypes have been described which are considered to fall under the umbrella of alternatively activated M2 macrophages (reviewed in [31,37]). An example of this occurs with administration of IL33 (which is functionally atheroprotective [38]) to genetically obese diabetic (ob/ob) mice, resulting in increased production of Th2 cytokines and polarisation of adipose tissue macrophages to a CD206+ M2 phenotype [39].


Innate immunity and monocyte-macrophage activation in atherosclerosis.

Shalhoub J, Falck-Hansen MA, Davies AH, Monaco C - J Inflamm (Lond) (2011)

Macrophages have classically been described as M1 and M2. These two phenotypes differ substantially with respect to the expression of macrophage associated genes. More recently, Kadl et al have described a new subset termed MOX macrophages [36]. These are induced by an environment rich in structurally defined oxidation products such as oxidised 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC) and can be induced from an M1 or M2 phenotype. ARE, antioxidant responsive elements; ARG1, arginase 1; CCL, chemokine ligand; COX2, cyclo-oxygenase 2; CXCL, chemokine CXC motif ligand; FIZZ1, found in inflammatory zone 1; GR, galactose receptor; HO1, heme-oxygenase 1; IL, interleukin; IL1ra; interleukin 1 receptor antagonist; ILR2, interleukin 1 receptor type II, decoy receptor; iNOS, inducible nitric oxide synthase; NRF2, nuclear factor erythroid 2-like 2; SR, scavenger receptor; Ym1, chitinase 3-like 3 lectin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3094203&req=5

Figure 1: Macrophages have classically been described as M1 and M2. These two phenotypes differ substantially with respect to the expression of macrophage associated genes. More recently, Kadl et al have described a new subset termed MOX macrophages [36]. These are induced by an environment rich in structurally defined oxidation products such as oxidised 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC) and can be induced from an M1 or M2 phenotype. ARE, antioxidant responsive elements; ARG1, arginase 1; CCL, chemokine ligand; COX2, cyclo-oxygenase 2; CXCL, chemokine CXC motif ligand; FIZZ1, found in inflammatory zone 1; GR, galactose receptor; HO1, heme-oxygenase 1; IL, interleukin; IL1ra; interleukin 1 receptor antagonist; ILR2, interleukin 1 receptor type II, decoy receptor; iNOS, inducible nitric oxide synthase; NRF2, nuclear factor erythroid 2-like 2; SR, scavenger receptor; Ym1, chitinase 3-like 3 lectin.
Mentions: Macrophage phenotypic polarisation may have a role in the fate of an atherosclerotic plaque. The plaque is an environment with a strong skew towards Th1 lymphocytic responses, resulting in high levels of IFNγ [33,34] which could in theory privilege M1-type macrophage polarisation. However, studies thus far have demonstrated macrophage heterogeneity within atherosclerosis, supporting that both M1 and M2 macrophages are present in human and murine atherosclerotic lesions. In an ApoE-/- murine model of atherosclerosis, early lesions were seen to be infiltrated by M2 (arginase I+) macrophages [35]. As lesions progressed a phenotypic switch was observed, with an eventual predominance of M1 (arginase II+) macrophages. Upon exposure to the oxidised phospholipid 1-palmitoyl-2-arachidonoyl-sn-3-phosphorylcholine (oxPAPC), murine macrophages adopted a previously undescribed phenotype (Figure 1) [36]. A reduction in the expression of genes characteristic of both M1 and M2, coupled with an up-regulation of a unique redox gene signature that includes haemoxygenase 1, was observed. This population, termed Mox macrophages, are nuclear factor erythroid 2-like 2 (Nrf2)-dependent and have been shown to comprise approximately 30% of all macrophages in advanced atherosclerotic lesions of LDLR-/- mice [36]. A variety of subtypes have been described which are considered to fall under the umbrella of alternatively activated M2 macrophages (reviewed in [31,37]). An example of this occurs with administration of IL33 (which is functionally atheroprotective [38]) to genetically obese diabetic (ob/ob) mice, resulting in increased production of Th2 cytokines and polarisation of adipose tissue macrophages to a CD206+ M2 phenotype [39].

Bottom Line: Innate inflammation is a hallmark of both experimental and human atherosclerosis.The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets.Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cytokine Biology of Atherosclerosis, Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, UK. c.monaco@imperial.ac.uk.

ABSTRACT
Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

No MeSH data available.


Related in: MedlinePlus