Department of Pathology, University of São Paulo Medical School, Sao Paulo - SP CEP 01246-903, Brazil.
Hum Pathol. 2012 Oct;43(10):1601-10. doi: 10.1016/j.humpath.2011.11.017. Epub 2012 Mar 19.
Pulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule (P < .03) and C3a anaphylatoxin receptor (P < .008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule (P = .004), vascular cell adhesion molecule (P = .030), and Toll-like receptor 2 (P = .042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group (P = .015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis.
钩端螺旋体病的肺部受累在过去 20 年中报道越来越多，与疾病的严重程度和死亡率有关。钩端螺旋体病肺出血的发病机制尚不清楚。肺内皮细胞被认为是通过激活 Toll 样受体 2 或补体系统参与钩端螺旋体病肺受累发病机制的靶点，这会刺激细胞因子的释放，导致黏附分子的激活。本研究旨在探讨免疫途径以及细胞间和血管细胞黏附分子（细胞间黏附分子和血管细胞黏附分子）在钩端螺旋体病肺受累患者肺部的作用。我们研究了 18 例死于钩端螺旋体病的患者的肺部，并将其与 2 组对照进行了比较：正常和非传染性出血性肺部。通过免疫组织化学和图像分析，我们定量了小肺血管和肺泡隔中 C3a 过敏毒素受体、细胞间黏附分子、血管细胞黏附分子和 Toll 样受体 2 的表达。与正常和出血对照相比，钩端螺旋体病组的肺泡隔中细胞间黏附分子（P <.03）和 C3a 过敏毒素受体（P <.008）的表达增加。在钩端螺旋体病组的血管中，细胞间黏附分子（P =.004）、血管细胞黏附分子（P =.030）和 Toll 样受体 2（P =.042）的表达均高于正常组。与出血组相比，钩端螺旋体病组血管中的血管细胞黏附分子表达更高（P =.015）。我们的结果表明，免疫受体和黏附分子参与了钩端螺旋体病导致的肺出血现象。
