MARCO Is the Major Binding Receptor for Unopsonized Particles and Bacteria on Human Alveolar Macrophages

Abstract

Alveolar macrophages (AMs) avidly bind and ingest inhaled environmental particles and bacteria. To identify the particle binding receptor(s) on human AMs, we used functional screening of anti-human AM hybridomas and isolated a mAb, PLK-1, which inhibits AM binding of unopsonized particles (e.g., TiO2, latex beads; 63 ± 5 and 67 ± 4% inhibition, respectively, measured by flow cytometry; n = 11) and unopsonized bacteria (∼84 and 41% inhibition of Escherichia coli and Staphylococcus aureus binding by mAb PLK-1, respectively). The PLK-1 Ag was identified as the human class A scavenger receptor (SR) MARCO (macrophage receptor with collagenous structure) by observing specific immunolabeling of COS cells transfected with human MARCO (but not SR-AI/II) cDNA and by immunoprecipitation by PLK-1 of a protein of appropriate molecular mass (∼70 kDa) from both normal human bronchoalveolar lavage cells (>90% AMs) and human MARCO-transfected COS cells. PLK-1 also specifically inhibited particle binding by COS cells, only after transfection with human MARCO cDNA. Immunostaining showed specific labeling of AMs within human lung tissue, bronchoalveolar lavage samples, as well as macrophages in other sites (e.g., lymph node and liver). Using COS transfectants with different truncated forms of MARCO, allowed epitope mapping for the PLK-1 Ab to MARCO domain V between amino acid residues 420 and 431. A panel of Abs to various SRs identified expression on AMs, but failed to inhibit TiO2 or S. aureus binding. The data support a dominant role for MARCO in the human AM defense against inhaled particles and pathogens.

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma

“…The MARCO receptor binds environmental particles, bacteria, and oxidized lipids. 33,[47][48][49] The absence of MARCO leads to an increased inflammatory response suggesting MARCO modulates the immune response. 50,51 In lung alveolar macrophages increased MARCO expression polarized lung alveolar macrophages toward a profibrotic M2 phenotype.…”

The biodegradability of electrospun Dextran/PLGA scaffold in a fibroblast/macrophage co-culture

“…Understanding this process is important for designing future biomaterials for applications such as drug delivery systems targeting specific receptors [31]. Hitherto, most related studies have been focused on inhalable natural particles [32,33] and metallic bone substitutes [34,35]. In our investigation, we attempted to screen for some of the receptors that were previously shown to associate with biomaterial degradation and might be involved in scaffold degradation.…”

The P2X7-nonmuscle myosin membrane complex regulates phagocytosis of nonopsonized particles and bacteria by a pathway attenuated by extracellular ATP

“…1 Several scavenger receptors have also been identified that directly interact with nonopsonized particles, and these are broadly classified as class A (macrophage receptor with collagenous structure) and class B (2 transmembrane receptors), 2 whereas among others is the C-type lectin-like receptor, dectin-1. [3][4][5][6][7][8][9] Assays for these scavenger receptors use nonselective inhibitors, polyinosinic acid, liposomes containing phosphatidylserine, oxidized low-density lipoprotein, or fucoidan, to inhibit this pathway. Phagocytosis of particles is accompanied by major rearrangements in the actin-myosin cytoskeleton, but there is little information on how scavenger receptors interact with proteins of the cytoskeleton.…”