Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.
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.
Madan
T
T
Centre for Biochemical Technology, Council for Scientific and Industrial Research, Delhi, India.
Kishore
U
U
Singh
M
M
Strong
P
P
Clark
H
H
Hussain
E M
EM
Reid
K B
KB
Sarma
P U
PU
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*
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