Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D.
Lung surfactant proteins (SP) A and D are calcium-dependent carbohydrate-binding proteins. In addition to playing multiple roles in innate immune defense such as bacterial aggregation and modulation of leukocyte function, SP-A and SP-D have also been implicated in the allergic response. They interact with a wide range of inhaled allergens, competing with their binding to cell-sequestered IgE resulting in inhibition of mast cell degranulation, and exogenous administration of SP-A and SP-D diminishes allergic hypersensitivity in vivo. House dust mite allergens are a major cause of allergic asthma in the western world, and here we confirm the interaction of SP-A and SP-D with two major mite allergens, Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1, and show that the cysteine protease activity of these allergens results in the degradation of SP-A and SP-D under physiological conditions, with multiple sites of cleavage. A recombinant fragment of SP-D that is effective in diminishing allergic hypersensitivity in mouse models of dust mite allergy was more susceptible to degradation than the native full-length protein. Degradation was enhanced in the absence of calcium, with different sites of cleavage, indicating that the calcium associated with SP-A and SP-D influences accessibility to the allergens. Degradation of SP-A and SP-D was associated with diminished binding to carbohydrates and to D. pteronyssinus 1 itself and diminished capacity to agglutinate bacteria. Thus, the degradation and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of these common dust mite allergens.
Deb
Roona
R
MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Shakib
Farouk
F
Reid
Kenneth
K
Clark
Howard
H
D000371:Agglutination; D000485:Allergens / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000378:metabolism*; D060829:Arthropod Proteins; D001249:Asthma / Q000201:enzymology / Q000276:immunology; D001419:Bacteria / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D040001:Dermatophagoides farinae / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology / Q000378:metabolism*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; C451162:Dermatophagoides pteronyssinus antigen p 1; D002118:Calcium