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

Alveolar macrophages (AMs) avidly bind and ingest unopsonized environmental particles and bacteria through scavenger-type receptors (SRs). AMs from mi ce with a genetic deletion of the major macrophage SR (types AI and AII; SR -/-) showed no decrease in particle binding compared with SR+/+ mice, sugge sting that other SRs are involved. To identify these receptors, we generate d a monoclonal antibody (mAb), PAL-1, that inhibits hamster AM binding of u nopsonized particles (TiO2, Fe2O3, and latex beads; 66 +/- 5, 77 +/- 2, and 85 +/- 2% inhibition, respectively, measured by flow cytometry). This anti body identifies a protein of similar to 70 kD on the AM surface (immunoprec ipitation) that is expressed by AMs and other macrophages in situ. A cDNA c lone 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 scaveng er 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 Esch erichia coli and Staphylococcus aureus binding by mAb PAL-1). A polyclonal antibody to human MARCO identified the expected similar to 70-kD band on We stern blots of lysates of normal bronchoalveolar lavage (BAL) cells (>90% A Ms) and showed strong immunolabeling of human AMs in BAL cytocentrifuge pre parations and within lung tissue specimens. In normal mouse AMs, the anti-M ARCO mAb ED31 also showed immunoreactivity and inhibited binding of unopson ized particles (e.g., TiO2 similar to 40%) and bacteria. The novel function of binding unopsonized environmental dusts and pathogens suggests an impor tant role for MARCO in the lungs' response to inhaled particles.