Human lung surfactant protein A exists in several different oligomeric states: Oligomer size distribution varies between patient groups
Human lung surfactant protein A exists in several different oligomeric states: Oligomer size distribution varies between patient groups
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DOI：
10.1007/bf03401923
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发表时间：
1998-04-01
影响因子：
5.7
通讯作者：
Sim, RB
中科院分区：
文献类型：
--
作者：
Hickling, TP;Malhotra, R;Sim, RB
背景：肺表面活性蛋白A（SP-A）是由18条多肽链组成的复杂分子。在体内，SP-A可能通过表面碳水化合物与SP-A的凝集素结构域的相互作用与广泛的吸入材料结合，并介导它们与细胞的相互作用，作为天然防御系统的一部分。凝集素结构域的多样性提供了高亲和力结合碳水化合物轴承surfaces.Materials和方法：凝胶过滤分析进行支气管肺泡灌洗（BAL）液样本从三个病人组：肺泡蛋白沉积症（n = 12），桦树花粉过敏（n = 11），和健康志愿者（n = 4）。采用蔗糖密度梯度离心法测定SP-A低聚物的分子量。SP-A从脂质相溶解，比较寡聚状态与水溶性SP-A。结果：SP-A存在的完全组装的复合物与18条多肽链，但它也始终被发现在较小的寡聚体形式。这是真实的SP-A的水溶性和脂溶性部分。结论：分析的三个患者组显示了向低聚体形式的SP-A在以下序列中的转变：健康肺泡蛋白沉积症花粉过敏。预计解聚将导致对富含碳水化合物的表面的结合亲和力的丧失，以及生物功能的丧失或改变。虽然有许多复杂的因素参与过敏的建立，但SP-A在清除肺部潜在过敏原方面的参与减少可能是事件链中的早期步骤。
Background: Lung surfactant protein A (SP-A) is a complex molecule composed of up to 18 polypeptide chains. In vivo, SP-A probably binds to a wide range of inhaled materials via the interaction of surface carbohydrates with the lectin domains of SP-A and mediates their interaction with cells as part of a natural defense system. Multiplicity of lectin domains gives high-affinity binding to carbohydrate-bearing surfaces.Materials and Methods: Gel filtration analyses were performed on bronchoalveolar lavage (BAL) fluid samples from three patient groups: pulmonary alveolar proteinosis (n = 12), birch pollen allergy (n = 11), and healthy volunteers (n = 4). Sucrose density gradient centrifugation was employed to determine molecular weights of SP-A oligomers. SP-A was solubilized from the lipid phase to compare oligomeric state with that of water soluble SP-A.Results: SP-A exists as fully assembled complexes with 18 polypeptide chains, but it is also consistently found in smaller oligomeric forms. This is true for both the water- and lipid-soluble fractions of SP-A.Conclusion: The three patient groups analyzed show a shift towards lower oligomeric forms of SP-A in the following sequence: healthy-pulmonary alveolar proteinosis-pollen allergy. Depolymerization would be expected to lead to loss of binding affinity for carbohydrate rich surfaces, with loss or alteration of biological function. While there are many complex factors involved in the establishment of an allergy, it is possible that reduced participation of SP-A in clearing a potential allergen from the lungs could be an early step in the chain of events.