Baltadzhiev Ivan Georgiev, Delchev Slavi Dimitrov
Department of Infectious Diseases, Parasitology and Tropical Medicine, Medical University, Plovdiv, Bulgaria.
Folia Histochem Cytobiol. 2013;51(2):121-6. doi: 10.5603/FHC.2013.0019.
Mediterranean spotted fever (MSF) is widely prevalent in many endemic regions in Bulgaria. The disease is still not quite thoroughly studied as to some aspects of its pathogenesis and especially to issues that concern the crucial signals for apoptosis in the target microvascular endothelial cells. To study the expression of Bcl-2 family proteins and Caspase-3 in the dermal capillary endothelial cells from skin papules and in the eschar (tache noire) epidermal layers of patients with MSF so that we can establish apoptotic processes and the time of their occurrence and deployment. Immunohistochemical reactions for Bcl-2, Bax and Caspase-3 were obtained in slices of punch-biopsies taken from papules of the skin rash and from the eschars of eight patients with MSF. The average intensity of the reactions was compared with that in control punch-biopsy slices from four healthy subjects. MSF was etiologically confirmed in all patients by positive antibody response to a specific antigen, Rickettsia conorii, with indirect immunofluorescent assay performed by the Rickettsial Reference Laboratory. The immune reaction for Bcl-2 was found to be poorly expressed in the capillary endothelial cells of skin papules of patients without any differences from controls. The expression of Bax and Caspase-3 was strongly upregulated in comparison with the controls. The Bcl-2/Bax ratio was significantly decreased. Microvascular endothelial cells of the eschar showed similar changes. While the Bcl-2/Bax ratio decreased in the epidermal layers of the eschar "tache noire", there were no changes in the intensity of the immunoreactivity of Caspase-3 as compared with controls. The upregulation of Bax and Caspase-3 is an indication of ongoing apoptotic processes in the dermal microvascular endothelial cells of MSF patients. The epidermal layers of the eschar showed increased sensitivity to apoptosis, however, executive phase of apoptosis did not occur.
地中海斑疹热（MSF）在保加利亚的许多流行地区广泛存在。关于其发病机制的某些方面，尤其是与靶微血管内皮细胞凋亡的关键信号相关的问题，该疾病仍未得到充分研究。为了研究MSF患者皮肤丘疹的真皮毛细血管内皮细胞和焦痂（黑色焦痂）表皮层中Bcl-2家族蛋白和半胱天冬酶-3的表达，以便我们能够确定凋亡过程及其发生和发展的时间。对8例MSF患者皮疹丘疹和焦痂的打孔活检切片进行了Bcl-2、Bax和半胱天冬酶-3的免疫组织化学反应。将反应的平均强度与4名健康受试者的对照打孔活检切片进行比较。通过立克次体参考实验室进行的间接免疫荧光测定，对特定抗原康氏立克次体的阳性抗体反应在所有患者中病因学上确诊为MSF。发现Bcl-2的免疫反应在患者皮肤丘疹的毛细血管内皮细胞中表达较弱，与对照组无差异。与对照组相比，Bax和半胱天冬酶-3的表达强烈上调。Bcl-2/Bax比值显著降低。焦痂的微血管内皮细胞显示出类似的变化。虽然在黑色焦痂的表皮层中Bcl-2/Bax比值降低，但与对照组相比，半胱天冬酶-3免疫反应性的强度没有变化。Bax和半胱天冬酶-3的上调表明MSF患者真皮微血管内皮细胞中正在进行凋亡过程。焦痂的表皮层对凋亡的敏感性增加，然而，凋亡的执行阶段并未发生。
