The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/5/1497/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 9, May 3, 1999 1497-1506

Articles

Role of the Scavenger Receptor MARCO in Alveolar Macrophage Binding of Unopsonized Environmental Particles

Aiyappa Palecanda*, Joseph Paulauskis*, Eiman Al-Mutairi*, Amy Imrich*, Guozhong Qin*, Hiroshi Suzuki§, Tatsuhiko Kodama§, Karl Tryggvason||, Henry Koziel, and Lester Kobzik{ddagger}

From the * Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the {ddagger} Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115; the § Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153, Japan; the || Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; and the Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215

Alveolar macrophages (AMs) avidly bind and ingest unopsonized environmental particles and bacteria through scavenger-type receptors (SRs). AMs from mice with a genetic deletion of the major macrophage SR (types AI and AII; SR–/–) showed no decrease in particle binding compared with SR+/+ mice, suggesting that other SRs are involved. To identify these receptors, we generated a monoclonal antibody (mAb), PAL-1, that inhibits hamster AM binding of unopsonized particles (TiO2, Fe2O3, and latex beads; 66 ± 5, 77 ± 2, and 85 ± 2% inhibition, respectively, measured by flow cytometry). This antibody identifies a protein of ~70 kD on the AM surface (immunoprecipitation) that is expressed by AMs and other macrophages in situ. A cDNA clone encoding the mAb PAL-1–reactive protein isolated by means of COS cell expression was found to be 84 and 77% homologous to mouse and human scavenger receptor MARCO mRNA, respectively. Transfection of COS cells with MARCO cDNA conferred mAb-inhibitable TiO2 binding. Hamster MARCO also mediates AM binding of unopsonized bacteria (67 ± 5 and 47 ± 4% inhibition of Escherichia coli and Staphylococcus aureus binding by mAb PAL-1). A polyclonal antibody to human MARCO identified the expected ~70-kD band on Western blots of lysates of normal bronchoalveolar lavage (BAL) cells (>90% AMs) and showed strong immunolabeling of human AMs in BAL cytocentrifuge preparations and within lung tissue specimens. In normal mouse AMs, the anti-MARCO mAb ED31 also showed immunoreactivity and inhibited binding of unopsonized particles (e.g., TiO2 ~40%) and bacteria. The novel function of binding unopsonized environmental dusts and pathogens suggests an important role for MARCO in the lungs' response to inhaled particles.

Key Words: MARCO • alveolar • macrophage • unopsonized • environmental particle

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

This study complies with National Institutes of Health guidelines and was approved by the Institutional Review Committees on Animals of the Harvard School of Public Health.

Abbreviations used: AM, alveolar macrophage; BAL, bronchoalveolar lavage; BSS, balanced salt solution; CS, chondroitin sulfate; PI, polyinosinic acid; RAS, right angle scatter; SR, scavenger receptor; SRCR, scavenger receptor cysteine-rich domain.


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