MARCO

Official Full Name

macrophage receptor with collagenous structure

Organism

Homo sapiens

GeneID

8685

Background

The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains. [provided by RefSeq, Jul 2008]

Synonyms

SR-A6; SCARA2;

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Detailed Information

The macrophage receptor with collagenous structure (MARCO) is a trimeric glycoprotein on the surface of macrophages and belongs to the Scavenger receptor (SR). MARCO has a conserved 110 amino acid fragment in the C-terminal specific domain, which is rich in cysteine and is therefore referred to as a cysteine-rich receptor domain and is directly or indirectly related to the defense function of the body. MARCO is mainly distributed on various macrophage membranes and participates in the body's immune response to inhaled particulate matter and pathogens. Its expression is often affected by bacteria, exogenous toxins and particles.

MARCO Mediates the Identification and Phagocytosis of Dust Particles

MARCO is the most important receptor for binding to non-opsonin-dependent particles (such as SiO2). It also interacts with a variety of receptors, including Toll-like receptors, to regulate the body's immune response. The exact function of SR is currently uncertain, but is considered to be an important part of the innate immune response, and its expression is generally up-regulated in the presence of infection. Due to the complex nature of SR, the researchers suggest that it may have multiple functions, including endocytosis, cell adhesion, cell transport, and intracellular signal transduction, and participate in the binding and uptake of polyanionic particles.

By immunoprecipitation, MARCO monoclonal antibody PAL-1 antibody binds to a protein of about 70 kD on the surface of macrophages, and its mRNA has high homology with the mRNA corresponding to human MARCO. At the same time, studies have shown that the use of cell transfection and co-immunoprecipitation to detect the interaction between human MARCO and dust particles also demonstrates that MARCO plays a crucial role in the body's defense against inhaled particles.

Figure 1. Role of Macrophages in Autoimmunity. (Gordon, et al. 2014)

The Role of MARCO in Silicosis

Silicosis is a systemic disease characterized by fibrosis of lung tissue caused by long-term inhalation of dust with a high level of silicon dioxide (SiO2). After entering the body, SiO2 dust first interacts with Alveolar macrophage (AM), including the recognition of particles by MARCO and the encapsulation and phagocytosis of macrophages. If SiO2 is not successfully removed from the lungs, it can cause a persistent inflammatory response that can eventually lead to pulmonary interstitial fibrosis.

Studies have shown that the use of C57BL /6 wild-type mice and MARCO - / - mice to determine the role of MARCO in the pathological changes of SiO2 induced lung, the results showed that the AM expression of mice treated with SiO2 increased MARCO, while phosphate buffer and TiO2 The treatment group MARCO did not increase; compared with wild mice, MARCO - / - mice exposed to SiO2 showed stronger inflammatory response and lung injury, but the degree of fibrosis was not significantly increased. Studies have shown that experiments using SR knockout mice did not reveal the formation of pulmonary fibrosis.

The study found that there was a positive correlation between the expression of macrophage SR1, MARCO and the apoptotic protein Caspase-3 on the AM surface of silicosis patients, indicating that SR-A is associated with AM death in silicosis patients. After the polymorphic guanine nucleotides of SD rats blocked the binding of MARCO to SiO2, the level of AM oxidative stress was significantly reduced, and the degree of pulmonary fibrosis was weakened, but inflammatory lesions still existed. Further studies have found that the reduction in fibrosis may be related to the inhibition of EMT by poly-guanine nucleotides. In addition, MARCO is also associated with susceptibility to chronic obstructive pulmonary disease, tuberculosis, and lung infections.

References:

Novakowski, K. E., Angela, H., Han, S. J., Dorrington, M. G., Yin, C., & Tu, Z., et al. (2016). A naturally-occurring transcript variant of marco reveals the srcr domain is critical for function:. Immunology & Cell Biology, 94(7), 646-655
Gordon, S. , & Annette Plüddemann. (2014). Chapter 11–role of macrophages in autoimmunity. Autoimmune Diseases, 161-174.
Lara, S. , Perez-Potti, André, Herda, L. M. , Adumeau, L. , Dawson, K. A. , & Yan, Y. . (2018). Differential recognition of nanoparticle protein corona and modified low density lipoprotein by macrophage receptor with collagenous structure. ACS Nano, acsnano.8b02014.

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