title: Aerosolized endotoxin is immediately bound by pulmonary surfactant protein D in vivo.
abstract: Collectins are carbohydrate binding proteins that are implicated in innate host defense. The lung collectins, surfactant proteins A and D (SP-A and SP-D), bind a variety of pathogens in vitro and influence phagocytosis by alveolar macrophages. In this report we show that SP-D binds endotoxin (lipopolysaccharide, LPS) in vivo in a rat model of acute respiratory distress syndrome (ARDS). Intratracheal aerosolization of LPS in rats resulted in the typical features of human ARDS. Total amounts of SP-D, as well as the carbohydrate binding properties of SP-D were measured in lung lavage as a function of time. The amount of SP-D did not change during 24 h. Interestingly, SP-D in lung lavage isolated from rats during the first 2 h after LPS treatment, was not able to bind to carbohydrate. Further analysis revealed that the carbohydrate binding sites of SP-D were occupied by LPS, suggesting that SP-D is an LPS scavenging molecule in vivo. Electron microscopic analysis indicated that, 1 h after LPS aerosolization, aggregates of SP-D with LPS were found in lysosomal structures in alveolar macrophages. We conclude that the lung collectin SP-D binds inhaled endotoxin in vivo, which may help to protect the lung from endotoxin-induced disease.
authors.affiliation: Department of Biochemistry and Cell Biology, Graduate School Animal Health, Faculty of Veterinary Medicine, P.O. Box 80.176, Utrecht University, 3508 TD, Utrecht, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: van Rozendaal
authors.forename: C H
authors.initials: CH
authors.lastname: van de Lest
authors.forename: M
authors.initials: M
authors.lastname: van Eijk
authors.forename: L M
authors.initials: LM
authors.lastname: van Golde
authors.forename: W F
authors.initials: WF
authors.lastname: Voorhout
authors.forename: H P
authors.initials: HP
authors.lastname: van Helden
authors.forename: H P
authors.initials: HP
authors.lastname: Haagsman
mesh_terms: D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D006651:Histocytochemistry; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008351:Mannans / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000378:metabolism; D013997:Time Factors; D014132:Trachea
chemical_list: D000336:Aerosols; D004731:Endotoxins; D006023:Glycoproteins; D008070:Lipopolysaccharides; D008351:Mannans; D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D016650:Fluorescein-5-isothiocyanate