Anton E S, Sandrock A W, Matthew W D
Duke University Medical Center, Department of Neurobiology, Durham, North Carolina 27710.
Dev Biol. 1994 Jul;164(1):133-46. doi: 10.1006/dbio.1994.1186.
Monoclonal antibodies that block the cellular function(s) of specific antigens can provide valuable probes for in vitro and in vivo bioassays. With the goal of understanding the molecular basis of neuron-Schwann cell interactions during development and regeneration, we have sought antibodies that interfere with the function of merosin, the predominant laminin isoform present in the Schwann cell basement membrane. To identify the biological functions of merosin in the peripheral nervous system, we studied Schwann cell migration and neurite outgrowth in vitro and nerve regeneration in vivo, in the presence and the absence of a monoclonal antibody that we believe binds to merosin, ARM-1 (Anti Rodent Merosin-1). The ARM-1 antibody blocked both neurite outgrowth and Schwann cell migration in vitro. This antibody also reduced neuritic branching in vitro. In vivo, the ARM-1 antibody blocked the regeneration of sympathetic nerve fibers in the rat iris. The blockade of neurite outgrowth and Schwann cell migration by ARM-1 antibody suggests that merosin is involved in facilitating the two most critical cellular events during the normal development and regeneration of peripheral nerves, i.e., axon growth and Schwann cell migration. Furthermore, the regulation of both Schwann cell migration and axon growth by the ARM-1 antigen implies that these two cellular events obey a common set of molecular signals during the development and regeneration of peripheral nerves.
阻断特定抗原细胞功能的单克隆抗体可为体外和体内生物测定提供有价值的探针。为了了解发育和再生过程中神经元与雪旺细胞相互作用的分子基础，我们一直在寻找能干扰merosin功能的抗体，merosin是雪旺细胞基底膜中主要的层粘连蛋白异构体。为了确定merosin在周围神经系统中的生物学功能，我们研究了在有和没有一种我们认为与merosin结合的单克隆抗体（ARM-1，抗啮齿动物merosin-1）的情况下，雪旺细胞在体外的迁移和神经突生长以及体内的神经再生。ARM-1抗体在体外阻断了神经突生长和雪旺细胞迁移。该抗体在体外也减少了神经突分支。在体内，ARM-1抗体阻断了大鼠虹膜中交感神经纤维的再生。ARM-1抗体对神经突生长和雪旺细胞迁移的阻断表明，merosin参与促进周围神经正常发育和再生过程中两个最关键的细胞事件，即轴突生长和雪旺细胞迁移。此外，ARM-1抗原对雪旺细胞迁移和轴突生长的调节意味着，在周围神经的发育和再生过程中，这两个细胞事件遵循一组共同的分子信号。
