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.
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3 May 1999
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May 03 1999
Role of the Scavenger Receptor MARCO in Alveolar Macrophage Binding of Unopsonized Environmental Particles
Aiyappa Palecanda,
Aiyappa Palecanda
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Joseph Paulauskis,
Joseph Paulauskis
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Eiman Al-Mutairi,
Eiman Al-Mutairi
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Amy Imrich,
Amy Imrich
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Guozhong Qin,
Guozhong Qin
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Hiroshi Suzuki,
Hiroshi Suzuki
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Tatsuhiko Kodama,
Tatsuhiko Kodama
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Karl Tryggvason,
Karl Tryggvason
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Henry Koziel,
Henry Koziel
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Lester Kobzik
Lester Kobzik
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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Aiyappa Palecanda
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Joseph Paulauskis
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Eiman Al-Mutairi
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Amy Imrich
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Guozhong Qin
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Hiroshi Suzuki
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Tatsuhiko Kodama
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Karl Tryggvason
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Henry Koziel
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
Lester Kobzik
From the *Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115; the ‡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
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: [email protected]
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.
Received:
February 17 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (9): 1497–1506.
Article history
Received:
February 17 1999
Citation
Aiyappa Palecanda, Joseph Paulauskis, Eiman Al-Mutairi, Amy Imrich, Guozhong Qin, Hiroshi Suzuki, Tatsuhiko Kodama, Karl Tryggvason, Henry Koziel, Lester Kobzik; Role of the Scavenger Receptor MARCO in Alveolar Macrophage Binding of Unopsonized Environmental Particles . J Exp Med 3 May 1999; 189 (9): 1497–1506. doi: https://doi.org/10.1084/jem.189.9.1497
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