Ortiz-Ordóñez J C, Sechelski J B, Seed J R
Biochemistry Unit, Centro Internacional de Entrenamiento, e Investigaciones Médicas, CIDEIM, Cali, Colombia.
J Parasitol. 1994 Dec;80(6):924-30.
Resistance to lysis by human serum (HS) is an important parameter used to distinguish Trypanosoma brucei brucei from both Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Neither the exact nature of the trypanolytic factor (TLF) nor the mechanism of action by which HS lyses susceptible trypanosomes is well understood. This report tries to elucidate the role played by the variable surface glycoprotein (VSG) coat and trypanosome surface-related processes in the mechanism of HS lysis of HS-sensitive (HSS) and HS-resistant (HSR) trypanosomes. Procyclic forms of T. brucei gambiense transformed from either HSS or HSR bloodstream stages were found to be HSR. These procyclic forms were shown to have lost their VSG coat. However, the addition of excess soluble VSG from HSS trypanosomes did not block lysis of HSS trypanosomes. Human serum lysis was significantly inhibited if the trypanosomes were incubated with membrane stabilizers, i.e., including cytochalasins (B, D, and E specifically), zinc acetate, vinblastine, and benzyl alcohol, or with the lysosomotropic agents ammonium chloride and chloroquine. The inhibition exerted by these compounds was always reversible. The results in this report, taken together, strengthen the hypothesis that the lytic factor interacts with and moves along the trypanosome surface to be internalized eventually.
对人血清（HS）裂解的抗性是用于区分布氏布氏锥虫与罗德西亚布氏锥虫和冈比亚布氏锥虫的一个重要参数。无论是锥虫溶解因子（TLF）的确切性质，还是HS裂解易感锥虫的作用机制，都尚未完全了解。本报告试图阐明可变表面糖蛋白（VSG）外衣和锥虫表面相关过程在HS敏感（HSS）和HS抗性（HSR）锥虫的HS裂解机制中所起的作用。从HSS或HSR血流阶段转化而来的冈比亚布氏锥虫的前循环型被发现是HSR。这些前循环型被证明已经失去了它们的VSG外衣。然而，添加来自HSS锥虫的过量可溶性VSG并没有阻止HSS锥虫的裂解。如果将锥虫与膜稳定剂（即包括细胞松弛素（特别是B、D和E）、醋酸锌、长春碱和苯甲醇）或与溶酶体促渗剂氯化铵和氯喹一起孵育，人血清裂解会受到显著抑制。这些化合物所施加的抑制总是可逆的。本报告中的结果综合起来，强化了这样一种假说，即裂解因子与锥虫表面相互作用并沿着锥虫表面移动，最终被内化。
