López S M, Pérez-Pérez M, Márquez J M, Naves F J, Represa J, Vega J A
Servicio de Cirugía Plástica y Reparadora, Hospital Central de Asturias, Oviedo, Spain.
Anat Rec. 1998 Jul;251(3):371-83. doi: 10.1002/(SICI)1097-0185(199807)251:3<371::AID-AR13>3.0.CO;2-L.
Human skin, including nerves and sensory corpuscles, displays immunoreactivity (IR) for low- (p75) and high-affinity (TrkA-like) receptors for nerve growth factor (NGF), the best characterized member of the family of neurotrophins. This study was designed to analyze the changes induced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to nerves and sensory corpuscles. Skin biopsy samples were obtained from 1) the hand and toes of normal subjects, 2) below the level of the lesion of patients with spinal cord injury affecting dorsal and lateral funiculi, 3) the cutaneous territory of entrapped peripheral nerves (median and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalin-fixed and paraffin-embedded, cut in serial sections, and processed for immunohistochemistry using antibodies against human p75 and TrkA proteins. The percentage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis. Spinal cord severance causes a decrease in p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands), both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory of entrapped nerves. Finally, in subjects with sectioned-grafted nerves, p75 IR was found close to controls in nerves, reduced in Meissner corpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA-like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups. Present results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of axonal continuity independently of possible restoration of axonal integrity due to grafts; 2) expression of TrkA-like IR in nerves and sensory corpuscles is sensitive only to nerve transection; 3) the corpuscular Schwann-related cells are the only cells involved in the above modifications, the perineurial cells remaining unchanged; 4) the expression of p75 and TrkA-like IR by Merkel cells is independent of normal innervation; 5) an adequate innervation of the skin seems to be necessary for the expression of p75 but not TrkA-like in nonneuronal cells, especially in the epidermis. A role for NGF in the maintenance of epidermis integrity is discussed.
人类皮肤，包括神经和感觉小体，对神经生长因子（NGF）的低亲和力（p75）和高亲和力（TrkA样）受体表现出免疫反应性（IR），NGF是神经营养因子家族中特征最明确的成员。本研究旨在分析脊髓和周围神经损伤引起的手指皮肤神经营养因子受体表达的变化，特别关注神经和感觉小体。皮肤活检样本取自：1）正常受试者的手部和脚趾；2）脊髓损伤累及背侧和外侧索患者损伤平面以下部位；3）受压周围神经（正中神经和尺神经）的皮肤区域；4）切断并移植神经（正中神经）的皮肤区域。样本用福尔马林固定、石蜡包埋，连续切片，并用抗人p75和TrkA蛋白的抗体进行免疫组织化学处理。使用定量图像分析评估显示p75和TrkA样免疫反应性的感觉小体的百分比，以及其中产生的免疫反应性强度。脊髓横断导致梅克尔小体和环层小体中p75免疫反应性降低，而TrkA样免疫反应性没有变化。在其他非神经组织（即表皮、汗腺）中，p75和TrkA样免疫反应性均减弱甚至缺失。在受压神经区域的皮肤中也出现了类似但更严重的变化。最后，在切断并移植神经的受试者中，发现神经中的p75免疫反应性接近对照组，梅克尔小体中降低，环层小体的内核中缺失；TrkA样免疫反应性存在于神经束膜、一小部分梅克尔小体（约7%）以及环层小体的外核和被膜中。在非神经组织中，p75免疫反应性几乎不存在，而TrkA样免疫反应性没有变化。不同组的默克尔细胞中未观察到神经营养因子受体表达的变化。目前的结果表明：1）人类皮肤感觉小体中神经p75免疫反应性的表达对中枢去传入、轴突运输的阻断或困难以及轴突连续性的破坏敏感，而与由于移植可能恢复的轴突完整性无关；2）神经和感觉小体中TrkA样免疫反应性的表达仅对神经横断敏感；3）与雪旺细胞相关的小体细胞是参与上述变化的唯一细胞，神经束膜细胞保持不变；4）默克尔细胞中p75和TrkA样免疫反应性的表达与正常神经支配无关；5）皮肤的充分神经支配似乎是在非神经元细胞中，尤其是在表皮中表达p75而不是TrkA样所必需的。讨论了NGF在维持表皮完整性中的作用。
