Alternative titles; symbols
HGNC Approved Gene Symbol: MARCO
Cytogenetic location: 2q14.2 Genomic coordinates (GRCh38): 2:118,942,194-118,994,660 (from NCBI)
Macrophages are mediators of nonspecific host defense that bind pathogens either directly or after the pathogens have been coated with antibody or complement. Elomaa et al. (1995) identified a novel mouse plasma membrane protein, called Marco, in subpopulations of macrophages in the spleen and the medullary cord of lymph nodes. No expression was observed in macrophages of liver or lung. Transfected COS cells synthesized a protein that bound labeled bacteria. By screening human liver and spleen cDNA libraries with a murine Marco cDNA probe and by genomic clone analysis, Elomaa et al. (1998) obtained a cDNA encoding a deduced 520-amino acid transmembrane protein. Sequence analysis showed a spacer domain with 2 potential glycosylation sites, an extracellular collagenous domain with glycine repeats, and a cysteine-rich domain at the extracellular C terminus. They determined that the bacteria-binding region of MARCO is localized proximal to the cysteine-rich domain. In situ hybridization analysis in tissues from neonates who had died from sepsis revealed expression in thymus, intestine, kidney, and liver but not in lung. The authors noted that expression outside of spleen and medullary cord of lymph nodes may have been due to infection since mice that develop endotoxic shock also express Marco in lung and liver macrophages after Klebsiella infection. Binding analyses determined that cells expressing MARCO bind gram-positive and gram-negative bacteria.
By analysis of genomic clones, Kangas et al. (1999) determined that mouse and human MARCO have 17 exons, with the collagenous domain encoded by exons 4 through 15; each of these 12 exons is an exact multiple of 9 bp, which is typical for fibrillar collagen genes.
By FISH, Kangas et al. (1999) mapped the human MARCO gene to chromosome 2q12-q13. They mapped the mouse Marco gene to a syntenic region on chromosome 1, the distal end of the E4 band.
Using a murine model of pneumococcal pneumonia, Arredouani et al. (2004) found that Marco -/- mice had impaired ability to clear bacteria from lungs, increased pulmonary inflammation and cytokine release, and diminished survival compared with wildtype mice. Marco -/- mice also had an increased inflammatory response to inert environmental dust. Mutant alveolar macrophages had a dramatic impairment in their ability to bind Streptococcus pneumoniae in vitro and to take up unopsonized particles in vivo. Arredouani et al. (2004) concluded that MARCO has an important role in mounting an efficient and appropriately regulated immune response against inhaled particles and pathogens.
Dorrington et al. (2013) compared the ability of knockout mice deficient for scavenger receptor Sra (MSR1; 153622), mannose receptor (MRC1; 153618), or Marco to clear Streptococcus pneumoniae from the nasopharynx. They observed that only the Marco-deficient mice had impaired clearance. Marco-deficient mice had abrogated cytokine production and cellular recruitment to the nasopharynx following colonization. Macrophages from Marco -/- mice are deficient in cytokine and chemokine production, including type I interferons (e.g., IFNB, 147640). Marco is also required for maximal Tlr2 (603028)- and Nod2 (605956)-dependent Nfkb (see 164011) activation and signaling that ultimately results in bacterial clearance. Dorrington et al. (2013) concluded that MARCO is critical for clearance of pneumococcus from the nasopharynx and preventing its spread to the lung.
Arredouani, M., Yang, Z., Ning, Y. Y., Qin, G., Soininen, R., Tryggvason, K., Kobzik, L. The scavenger receptor MARCO is required for lung defense against Pneumococcal pneumonia and inhaled particles. J. Exp. Med. 200: 267-272, 2004. [PubMed: 15263032] [Full Text: https://doi.org/10.1084/jem.20040731]
Dorrington, M. G., Roche, A. M., Chauvin, S. E., Tu, Z., Mossman, K. L., Weiser, J. N., Bowdish, D. M. E. MARCO is required for TLR2- and Nod2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx. J. Immun. 190: 250-258, 2013. [PubMed: 23197261] [Full Text: https://doi.org/10.4049/jimmunol.1202113]
Elomaa, O., Kangas, M., Sahlberg, C., Tuukkanen, J., Sormunen, R., Liakka, A., Thesleff, I., Kraal, G., Tryggvason, K. Cloning of a novel bacteria-binding receptor structurally related to scavenger receptors and expressed in a subset of macrophages. Cell 80: 603-609, 1995. [PubMed: 7867067] [Full Text: https://doi.org/10.1016/0092-8674(95)90514-6]
Elomaa, O., Sankala, M., Pikkarainen, T., Bergmann, U., Tuuttila, A., Raatikainen-Ahokas, A., Sariola, H., Tryggvason, K. Structure of the human macrophage MARCO receptor and characterization of its bacteria-binding region. J. Biol. Chem. 273: 4530-4538, 1998. [PubMed: 9468508] [Full Text: https://doi.org/10.1074/jbc.273.8.4530]
Kangas, M., Brannstrom, A., Elomaa, O., Matsuda, Y., Eddy, R., Shows, T. B., Tryggvason, K. Structure and chromosomal localization of the human and murine genes for the macrophage MARCO receptor. Genomics 58: 82-89, 1999. [PubMed: 10331948] [Full Text: https://doi.org/10.1006/geno.1999.5811]