title: 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 ( approximately 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 (approximately 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.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Arredouani
authors.forename: Aiyappa
authors.initials: A
authors.lastname: Palecanda
authors.forename: Henry
authors.initials: H
authors.lastname: Koziel
authors.forename: Yuh-Ching
authors.initials: YC
authors.lastname: Huang
authors.forename: Amy
authors.initials: A
authors.lastname: Imrich
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Sulahian
authors.forename: Yao Yu
authors.initials: YY
authors.lastname: Ning
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.forename: Timo
authors.initials: T
authors.lastname: Pikkarainen
authors.forename: Marko
authors.initials: M
authors.lastname: Sankala
authors.forename: Sara O
authors.initials: SO
authors.lastname: Vargas
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D018797:Cell Cycle Proteins / Q000502:physiology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology*; D010587:Phagocytosis; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000502:physiology; D011971:Receptors, Immunologic / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D014025:Titanium / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000911:Antibodies, Monoclonal; D018797:Cell Cycle Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; D014025:Titanium; D000097869:Polo-Like Kinase 1; C490460:MARCO protein, human; C009495:titanium dioxide