title: Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.
abstract: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (AFU:). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by AFU: antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of AFU:-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.
authors.affiliation: Centre for Biochemical Technology, Council for Scientific and Industrial Research, Delhi, India.
authors.forename: T
authors.initials: T
authors.lastname: Madan
authors.forename: U
authors.initials: U
authors.lastname: Kishore
authors.forename: M
authors.initials: M
authors.lastname: Singh
authors.forename: P
authors.initials: P
authors.lastname: Strong
authors.forename: H
authors.initials: H
authors.lastname: Clark
authors.forename: E M
authors.initials: EM
authors.lastname: Hussain
authors.forename: K B
authors.initials: KB
authors.lastname: Reid
authors.forename: P U
authors.initials: PU
authors.lastname: Sarma
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000209:etiology; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010544:Peroxidases / Q000378:metabolism; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D016207:Cytokines; D006023:Glycoproteins; D007074:Immunoglobulin G; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D007073:Immunoglobulin E; D047209:Eosinophil Peroxidase; D010544:Peroxidases