Role of the scavenger receptor MARCO in alveolar macrophage binding of unopsonized environmental particles

被引:175
作者
Palecanda, A
Paulauskis, J
Al-Mutairi, E
Imrich, A
Qin, GZ
Suzuki, H
Kodama, T
Tryggvason, K
Koziel, H
Kobzik, L
机构
[1] Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[3] Univ Tokyo, Adv Sci & Technol Res Ctr, Dept Mol Biol & Med, Tokyo 153, Japan
[4] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden
[5] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA
关键词
MARCO; alveolar; macrophage; unopsonized; environmental particle;
D O I
10.1084/jem.189.9.1497
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 similar to 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 similar to 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 similar to 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.
引用
收藏
页码:1497 / 1506
页数:10
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