Lung Surfactant Proteins (SP) -A and -D are calcium-dependent carbohydrate-binding proteins. In addition to playing multiple roles in innate immune defence 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 (Der p) 1 and Dermatophagoides farinae (Der f) 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 Der p 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.
- 1 decade agoFavorite Answer
肺Surfactant蛋白質(SP) -A和D是依靠鈣的捆碳水化合物的蛋白質。 除在象細菌的集中那樣的天生免疫的防禦裡扮演多個角色之外， 並且調製的白細胞功能，SP一和SP-D也和這過敏症回應有牽連是。 他們與大範圍吸入的變態回應原相互作用， 導致抑制的桅細胞degranulation 和外源管理的SP的同給細胞捆競爭使IgE退隱一和SP-D在活體內減少過敏症超靈敏度。 房子灰塵一點點變態回應原是一個在西方的世界的過敏症的氣喘病的主要的原因， 並且這裡，我們確認相互作用的SP一和有兩主要一點點變態回應原Dermatophagoides pteronyssinus(Der便士)的SP-D 1和Dermatophagoides farinae(Der f) 1 和顯示那那些cysteine蛋白酵活動的這幾次變態回應原導致墮落的SP一和SP-D， 在生理的狀況下，帶有分裂的多個場所。 一個用老鼠在減少過敏症的超靈敏度過程中有效的SP-D的recombinant碎片灰塵一點點過敏性回應的模型， 比本地全長蛋白質對墮落敏感。 墮落被缺乏鈣的情況下提升， 隨著不同站點的分裂，正在表明時，那些鈣與SP相關一和SP-D 影響去那些變態回應原的可接近。 墮落的SP一和SP-D與縮小有關給碳水化合物捆，和給1便士的它自己的Der，並且減少能力使細菌黏結。 因此那些墮落和隨之而來失活的SP一和SP-D可能是要解釋有效allergenicity的這幾次普通灰塵一點點變態回應原的小說機製。Source(s): 自己