Lung macrophage uptake of unopsonized environmental particulates. Role of scavenger-type receptors.
The receptors responsible for avid alveolar macrophage (AM) phagocytosis of unopsonized environmental particulates have not been well defined. This study used flow cytometry to quantitate the effects of a panel of soluble ligands for macrophage adhesion receptors on AM binding of unopsonized environmental dusts (titanium dioxide, TiO2; iron oxide, Fe2O3; alpha-quartz, SiO2; diesel engine exhaust dust) or fluorescent latex beads. Polyanionic ligands of the macrophage scavenger receptor (SR) for acetylated-LDL caused marked inhibition of AM binding of the oxide particles and latex beads (e.g., TiO2 binding; polyinosinic acid (polyl), 10 micrograms/ml: 70.2 +/- 1.5% inhibition, mean +/- SE, n = 11). In contrast, no inhibition was seen with the polyanions heparin and chondroitin sulfate (chond-S), or dextran, consistent with the known inhibitor profile of macrophage SRs for acetylated-LDL AM uptake of latex or SiO2 beads instilled into lungs of hamsters was inhibited by administration of polyl but not chondroitin sulfate (AM beads per cell: control, 6.1 +/- 0.7; polyl, 3.5 +/- 0.2; chond-S, 5.1 +/- 0.7, n > or = 4, p < 0.05 for control vs polyl) indicating macrophages SRs operate in vivo as well as in vitro. In contrast, AM binding of the carbonaceous diesel dust particles was not inhibited by any ligand tested. AM uptake of unopsonized TiO2, SR ligands or acetylated LDL caused no significant activation of AM respiratory burst or TNF production, consistent with past observations that opsonin-independent phagocytosis of inert particles by normal AMs is not accompanied by pro-inflammatory activation. These data implicate macrophage-type SRs in AM binding of charged environmental particles and indicate that distinct mechanisms mediate binding of carbonaceous dusts.
Kobzik
L
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Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
D000393:Air Pollutants / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D006224:Cricetinae; D005290:Ferric Compounds / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D011791:Quartz / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014025:Titanium / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity
D000393:Air Pollutants; D005290:Ferric Compounds; D008565:Membrane Proteins; D009895:Opsonin Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D001335:Vehicle Emissions; D011791:Quartz; C009495:titanium dioxide; C000499:ferric oxide; D014025:Titanium; D002118:Calcium