Kishor Uday, Madan Taruna, Sarma P Usha, Singh Mamta, Urban Britta C, Reid Kenneth B M
Department of Biochemistry, University of Oxford, UK.
Immunobiology. 2002 Sep;205(4-5):610-8. doi: 10.1078/0171-2985-00158.
Pulmonary surfactant proteins, SP-A and SP-D, are immune molecules which can directly interact with pathogens and allergens, stimulate immune cells and manipulate cytokine and chemokine profiles during host's immune response. Using an opportunistic fungal pathogen Aspergillus fumigatus (Afu), we have attempted to understand participation of SP-A and SP-D in the host immunity. Afu causes a systemic infection via lungs, called invasive aspergillosis (IPA) in immunocompromised subjects. In the immunocompetent subjects, it can cause an allergic disorder, called allergic bronchopulmonary aspergillosis (ABPA). Therapeutic administration of these proteins in a murine model of IPA can rescue mice from death. Treating mice, having ABPA, can suppress IgE levels, eosinophilia, pulmonary cellular infiltration and cause a marked shift from a pathogenic Th2 to a protective Th1 cytokine profile. These results highlight the potential of SP-A, SP-D and their recombinant forms, as novel therapeutics for lung allergy and infection.
肺表面活性蛋白SP - A和SP - D是免疫分子，它们可直接与病原体和过敏原相互作用，刺激免疫细胞，并在宿主免疫反应过程中调控细胞因子和趋化因子谱。我们利用机会性真菌病原体烟曲霉（Afu），试图了解SP - A和SP - D在宿主免疫中的作用。Afu通过肺部引发全身感染，在免疫功能低下的个体中称为侵袭性曲霉病（IPA）。在免疫功能正常的个体中，它可引发一种过敏性疾病，称为变应性支气管肺曲霉病（ABPA）。在IPA小鼠模型中对这些蛋白进行治疗性给药可使小鼠免于死亡。治疗患有ABPA的小鼠可抑制IgE水平、嗜酸性粒细胞增多、肺部细胞浸润，并使致病性Th2细胞因子谱显著转变为保护性Th1细胞因子谱。这些结果凸显了SP - A、SP - D及其重组形式作为肺部过敏和感染新型治疗药物的潜力。
