Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D.

Abstract

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.

• Authors: Roona Deb, Farouk Shakib, Kenneth Reid, Howard Clark
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 51 Pg. 36808-19 (Dec 21 2007) ISSN: 0021-9258 [Print] United States
• PMID: 17848554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Antigens, Dermatophagoides
• Arthropod Proteins
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Protein D
• Immunoglobulin E
• Cysteine Endopeptidases
• Dermatophagoides farinae antigen f 1
• Dermatophagoides pteronyssinus antigen p 1
• Calcium

Topics

• Agglutination
• Allergens (immunology, metabolism)
• Animals
• Antigens, Dermatophagoides (immunology, metabolism)
• Arthropod Proteins
• Asthma (enzymology, immunology)
• Bacteria (immunology)
• Calcium (immunology, metabolism)
• Cell Degranulation
• Cysteine Endopeptidases (immunology, metabolism)
• Dermatophagoides farinae (immunology)
• Dermatophagoides pteronyssinus (immunology)
• Humans
• Immunity, Innate
• Immunoglobulin E (immunology, metabolism)
• Leukocytes (immunology, metabolism)
• Mast Cells (immunology, metabolism)
• Pulmonary Surfactant-Associated Protein A (immunology, metabolism)
• Pulmonary Surfactant-Associated Protein D (immunology, metabolism)