The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published 19 July 2004. doi:10.1084/jem.20040731
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 2, 267-272
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Brief Definitive Report

 The Scavenger Receptor MARCO Is Required for Lung Defense against Pneumococcal Pneumonia and Inhaled Particles

Mohamed Arredouani1, Zhiping Yang1, YaoYu Ning1, Guozhong Qin1, Raija Soininen3, Karl Tryggvason4, and Lester Kobzik1,2

1 Physiology Program, Harvard School of Public Health and 2 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
3 Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, 90014 Oulu, Finland
4 Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden

Address correspondence to Lester Kobzik, Physiology Program, Harvard School of Public Health, 665 Huntington Ave., SPH-II, Rm. 221, Boston, MA 02115. Phone: (617) 432-2247; Fax: (617) 432-0014; email: lkobzik{at}hsph.harvard.edu

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 TiO2 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.

Key Words: macrophage • phagocytosis • environment • innate immunity


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