title: MARCO, an innate activation marker of macrophages, is a class A scavenger receptor for Neisseria meningitidis.
abstract: 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. Neisseria meningitidis (NM) is a selective ligand for SR-A, but there is evidence for an additional SR-A-independent, polyanion-sensitive component for NM recognition. We therefore studied the relative contribution of MARCO and SR-A to binding of NM by resident and elicited peritoneal macrophages obtained from MARCO-/-, SR-A-/- and SR-A-MARCO-/- mice. Results confirmed that both mouse and human MARCO are able to bind NM independently of NM LPS. MARCO and SR-A contributed independently to NM binding, correlating with their expression levels in different cell populations, but neither of these two molecules was required for release of TNF-alpha and nitric oxide. We propose that the TLR-dependent induction of MARCO by innate immune stimulation enhances recognition and uptake of pathogenic organisms such as NM, thus contributing to host defence against infection.
authors.affiliation: Sir William Dunn School of Pathology, Oxford, UK.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Yunying
authors.initials: Y
authors.lastname: Chen
authors.forename: Marko
authors.initials: M
authors.lastname: Sankala
authors.forename: Leanne
authors.initials: L
authors.lastname: Peiser
authors.forename: Timo
authors.initials: T
authors.lastname: Pikkarainen
authors.forename: Georg
authors.initials: G
authors.lastname: Kraal
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
mesh_terms: D000818:Animals; D015415:Biomarkers; D005434:Flow Cytometry; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009345:Neisseria meningitidis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
chemical_list: D015415:Biomarkers; C490460:MARCO protein, human; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A