title: Alveolar macrophages bind and phagocytose allergen-containing pollen starch granules via C-type lectin and integrin receptors: implications for airway inflammatory disease.
abstract: Recent studies suggest that IgE-independent mechanisms of airway inflammation contribute significantly to the pathophysiology of allergic airway inflammatory diseases such as asthma. Such mechanisms may involve direct interactions between inhaled allergens and cells of the respiratory tract such as macrophages, dendritic cells, and epithelial cells. In this study, we investigated receptor-mediated interactions occurring between alveolar macrophages and allergen-containing pollen starch granules (PSG). We report here that PSG are released from a range of grass species and are rapidly bound and phagocytosed by alveolar macrophages. Human monocyte-derived dendritic cells also bound PSG but no internalization was observed. Phagocytosis of PSG was dependent on Mg2+ and Ca2+ and was inhibited by neo-glycoproteins such as galactose-BSA and N-acetylgalactose-BSA. Partial inhibition of phagocytosis was also seen with the Arg-Gly-Asp-Ser (RGDS) motif and with an anti-CD18 mAb (OX42). The combination of both neo-glycoprotein and anti-CD18 achieved the greatest degree of inhibition (>90%). Together, these data suggest a role for both C-type lectins and beta2-integrins in the binding and internalization of PSG. The consequences of this interaction included a rapid up-regulation of inducible NO synthase mRNA and subsequent release of NO by alveolar macrophages. Thus, receptor-mediated recognition of inhaled allergenic particles by alveolar macrophages may represent a potential mechanism for modulating the inflammatory response associated with allergic airway diseases such as asthma.
authors.affiliation: Department of Microbiology, University of Western Australia, Nedlands, Western Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Currie
authors.forename: G A
authors.initials: GA
authors.lastname: Stewart
authors.forename: A S
authors.initials: AS
authors.lastname: McWilliam
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000485:Allergens / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005690:Galactose / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism*; D037181:Lectins, C-Type; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008358:Mannose / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D037121:Plant Lectins; D011058:Pollen / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013213:Starch / Q000276:immunology* / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000485:Allergens; D002413:Cations, Divalent; C113583:Clecsf8 protein, mouse; D016023:Integrins; D037102:Lectins; D037181:Lectins, C-Type; D008565:Membrane Proteins; C079431:N-acetylgalactosamine-bovine serum albumin conjugate; D037121:Plant Lectins; D012333:RNA, Messenger; D012709:Serum Albumin; C039136:bovine serum albumin-galactose (39); C023840:mannose-bovine serum albumin conjugate; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D013213:Starch; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000116:Acetylgalactosamine; D008358:Mannose; D005690:Galactose