Disease relevance of Marco

• In vitro binding of Streptococcus pneumoniae and in vivo uptake of unopsonized particles by MARCO(-/-) AMs were dramatically impaired [1].
• In a murine model of pneumococcal pneumonia, MARCO(-/-) mice displayed an impaired ability to clear bacteria from the lungs, increased pulmonary inflammation and cytokine release, and diminished survival [1].
• We used MARCO-deficient mice to directly test the in vivo role of AM MARCO in innate defense against pneumococcal infection and environmental particles [1].
• During bacillus Calmette-Guérin (BCG) infection, during bacterial sepsis, or after the injection of purified LPS, however, the expression of MARCO is rapidly induced on macrophages in other tissues, including Kupffer cells in the liver [2].
• MARCO, an innate activation marker of macrophages, is a class A scavenger receptor for Neisseria meningitidis [3].

High impact information on Marco

• Alveolar macrophages (AMs) express the class A scavenger receptor macrophage receptor with collagenous structure (MARCO), but its role in vivo in lung defense against bacteria and environmental particles has not been studied [1].
• MARCO(-/-) mice treated with the "inert" environmental particle TiO(2) showed enhanced inflammation and chemokine expression, indicating that MARCO-mediated clearance of inert particles by AMs prevents inflammatory responses otherwise initiated by other lung cells [1].
• The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs [4].
• Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes [4].
• Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia [4].

Biological context of Marco

• Whereas MARCO was involved in opsonin-independent phagocytosis in CpG-ODN-pretreated but not in IL-4-pretreated J774 cells, anti-SR-A Abs inhibited particle uptake in untreated and IL-4-pretreated but not in CpG-ODN-pretreated cells [5].
• Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs [4].
• Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation [4].
• By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells [4].
• The scavenger receptor-A I/II (SR-A) and macrophage receptor with collagenous domain (MARCO) share a common domain organisation and ligand repertoire, including selected polyanions and gram-positive and -negative organisms, but differ in fine specificity of ligand binding, tissue distribution and regulation [3].

Anatomical context of Marco

• SR-A and MARCO are regulated differently and mediate distinct negative and positive effects on IL-12 production in macrophages [5].
• In the present study, we found that genetic ablation of MARCO leads to changes in the organization of the splenic marginal zone, and causes a significant reduction in the size of the resident peritoneal macrophage population, possibly due to changes in adhesion and migration capacity [6].
• Rodd, Avram Goldstein, Alejandro Zaffaroni and Ting-Kai Li; and (5) Acetaldehyde increases dopaminergic transmission in the limbic system, by Milena Pisano and Marco Diana [7].
• Using the mouse macrophage cell line J774.2, it was shown that LPS stimulation up-regulates surface expression of MARCO in a dose- and time-dependent fashion [2].
• Murine MARCO has been identified recently in subsets of macrophages located in the peritoneum, marginal zone of the spleen, and the medullary cord of lymph nodes, where it has been proposed that it serves as a bacteria-binding receptor [8].

Associations of Marco with chemical compounds

• Two of those reacting with the C-terminal cysteine-rich domain block ligand binding of MARCO [2].
• We show that these stimuli regulate major histocompatibility complex type II (MHC-II) and costimulatory molecules differentially, as well as expression of the mannose receptor and of Mphi receptor with collagenous structure (MARCO), a distinct SR-A, which provides a selective marker for innate activation [9].
• Species-specific restriction of cell surface expression of mouse MARCO glycoprotein in murine cell lines [10].

Regulatory relationships of Marco

• Expression of SR-A was regulated in the opposite manner to MARCO or not affected [5].

Other interactions of Marco

• Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO [5].
• The macrophage class A scavenger receptors, macrophage receptor with a collagenous structure (MARCO) and type I/II class A scavenger receptor (SR-AI/II), share structural features and roles in host defense, but little is known about their regulation and signaling properties [5].
• PEMs from MARCO-deficient mice exhibited 2.7 times lower IL-12 production in responses to stimulation with LPS and IFN-gamma and lack of significant IL-12 production on stimulation with LPS alone [5].
• During ontogeny, the appearance and organization of the MARCO-expressing cells in the spleen precedes the appearance of other receptors on macrophages in the marginal zone, such as SIGNR1 and Siglec-1 [6].
• Liver-restricted induction of MARCO in mice with high-fat diet and portal endotoxaemia in ApoE(-/-) mice fed the high-fat diet suggest the possible involvement of endotoxin in the pathogenesis of NASH [11].

Analytical, diagnostic and therapeutic context of Marco

• Ligation of MARCO on mouse thioglycollate-elicited peritoneal macrophages (PEMs) with immobilized mAb costimulated IL-12 production, in contrast to previously reported inhibition by SR-AI/II [5].
• Inducible expression of macrophage receptor Marco by dendritic cells following phagocytic uptake of dead cells uncovered by oligonucleotide arrays [12].

References