Mapp P I, Kidd B L, Gibson S J, Terry J M, Revell P A, Ibrahim N B, Blake D R, Polak J M
Inflammation Group, London Hospital Medical College, U.K.
Neuroscience. 1990;37(1):143-53. doi: 10.1016/0306-4522(90)90199-e.
By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
借助针对神经纤维细胞质成分和已知存在于感觉神经或交感神经中的神经肽的抗血清，我们研究了正常和发炎的人类滑膜组织中总神经纤维和不同类型神经纤维的分布。滑膜样本在手术中取自五名正常人和五名类风湿性关节炎患者（年龄范围10 - 77岁）。为了描绘滑膜的整体神经支配情况，使用了针对一般神经元标记蛋白基因产物9.5的抗血清。使用P物质和降钙素基因相关肽抗血清来识别感觉纤维，使用神经肽Y的C末端侧翼肽抗血清来区分交感神经。在正常滑膜中，蛋白基因产物9.5免疫反应性纤维众多，特别是血管周围有密集的神经支配。游离的蛋白基因产物9.5免疫反应性纤维数量较少，但在所检查的所有滑膜中都存在，并且在许多情况下这些纤维延伸至内膜层。神经肽免疫染色主要见于血管周围网络。神经肽Y的C末端侧翼肽免疫反应性纤维仅位于血管周围，而游离纤维对P物质或降钙素基因相关肽呈免疫反应性。与游离的蛋白基因产物9.5免疫反应性纤维一样，表达P物质或降钙素基因相关肽免疫反应性的纤维常在内膜细胞层中见到。在类风湿性关节炎中，深层组织中可见到与正常滑膜中类似的神经支配，但在较浅的组织或内膜细胞层中，对蛋白基因产物9.5、神经肽Y的C末端侧翼肽、P物质或降钙素基因相关肽呈免疫反应性的纤维不可见。此外，患病组织深层组织中神经肽的免疫染色比正常对照弱。这些数据明确表明滑膜组织有丰富的神经支配，并证实了感觉神经和交感神经的存在。类风湿性关节炎中支配浅表滑膜的神经缺失可能表明P物质、降钙素基因相关肽和神经肽Y的C末端侧翼肽释放增加，使神经中的储存量减少到免疫细胞化学检测不到的水平。然而，由于在发炎组织中未见到蛋白基因产物9.5免疫反应性神经，很可能是滑膜生长超过了神经生长，并因此随着疾病进展神经结构局限于更深层组织。（摘要截断于400字）
