title: The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles.
abstract: Alveolar macrophages (AMs) express the class A scavenger receptor macrophage receptor with collagenous structure (MARCO), but its role in vivo in lung defense against bacteria and environmental particles has not been studied. We used MARCO-deficient mice to directly test the in vivo role of AM MARCO in innate defense against pneumococcal infection and environmental particles. In a murine model of pneumococcal pneumonia, MARCO(-/-) mice displayed an impaired ability to clear bacteria from the lungs, increased pulmonary inflammation and cytokine release, and diminished survival. In vitro binding of Streptococcus pneumoniae and in vivo uptake of unopsonized particles by MARCO(-/-) AMs were dramatically impaired. MARCO(-/-) mice treated with the "inert" environmental particle TiO(2) showed enhanced inflammation and chemokine expression, indicating that MARCO-mediated clearance of inert particles by AMs prevents inflammatory responses otherwise initiated by other lung cells. Our findings point to an important role of MARCO in mounting an efficient and appropriately regulated innate immune response against inhaled particles and airborne pathogens.
authors.affiliation: Physiology Program, Harvard School of Public Health, 665 Huntington Ave., SPH-II, Rm. 221, Boston, MA 02115, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Arredouani
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.forename: YaoYu
authors.initials: Y
authors.lastname: Ning
authors.forename: Guozhong
authors.initials: G
authors.lastname: Qin
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Lester
authors.initials: L
authors.lastname: Kobzik
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007113:Immunity, Innate; D007249:Inflammation; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000378:metabolism; D013997:Time Factors; D014025:Titanium / Q000494:pharmacology
chemical_list: D016207:Cytokines; C092228:Marco protein, mouse; D011971:Receptors, Immunologic; C009495:titanium dioxide; D014025:Titanium