Lin Peggy M, Wright Jo Rae
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1199-206. doi: 10.1152/ajplung.00188.2006.
Surfactant protein (SP)-A and SP-D, immunoglobulins, and complement all modulate inflammation within the lung by regulating pathogen clearance. For example, SP-A binds to and opsonizes a variety of bacteria and viruses, thereby enhancing their phagocytosis by innate immune cells such as alveolar macrophages. Immunoglobulins, which bind to antigen and facilitate Fc receptor-mediated phagocytosis, can also activate complement, a family of soluble proteins with multiple host defense functions. Previous studies showed that SP-A and complement protein C1q interact. Since complement protein C1q binds to IgG and IgM immune complexes, the hypothesis tested in this study was that SP-A, which is structurally homologous to C1q, also binds to IgG and affects its functions. SP-A binds to the Fc, rather than the Fab, region of IgG. Binding is calcium dependent but not inhibited by saccharides known to bind to SP-A's carbohydrate recognition domain. The binding of SP-A does not inhibit the formation of immune complexes or the binding of IgG to C1q. In contrast, SP-A enhances the uptake of IgG-coated erythrocytes, suggesting that SP-A might be influencing Fc receptor-mediated uptake. In summary, this study shows a novel interaction between SP-A and IgG and a functional consequence of the binding.
表面活性蛋白（SP）-A和SP-D、免疫球蛋白及补体均通过调节病原体清除来调控肺内炎症。例如，SP-A可结合并调理多种细菌和病毒，从而增强肺泡巨噬细胞等天然免疫细胞对它们的吞噬作用。能结合抗原并促进Fc受体介导的吞噬作用的免疫球蛋白，也可激活补体，补体是一类具有多种宿主防御功能的可溶性蛋白。既往研究表明，SP-A与补体蛋白C1q相互作用。由于补体蛋白C1q可结合IgG和IgM免疫复合物，本研究检验的假设是，结构与C1q同源的SP-A也可结合IgG并影响其功能。SP-A结合IgG的Fc区，而非Fab区。这种结合依赖钙，但不受已知可结合SP-A碳水化合物识别域的糖类抑制。SP-A的结合并不抑制免疫复合物的形成或IgG与C1q的结合。相反，SP-A可增强IgG包被红细胞的摄取，提示SP-A可能影响Fc受体介导的摄取。总之，本研究显示了SP-A与IgG之间的一种新型相互作用及其结合的功能后果。
