Garcia F U, Wojta J, Broadley K N, Davidson J M, Hoover R L
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232.
Am J Pathol. 1990 May;136(5):1125-35.
Bartonellosis, a biphasic disease caused by motile intracellular bacteria, produces in its tissue phase a characteristic dermal eruption (Verruga peruana) resulting from a pronounced endothelial cell proliferation. Bacteria are found in the interstitium and within the cytoplasm of endothelial cells (Rocha-Lima inclusion). The aim of this study was to determine if Bartonella bacilliformis produce a substance(s) that might be responsible for the vascular proliferation seen in the Verruga. This was assessed in an in vitro system using human endothelial cells and measuring proliferation as well as production of tissue type plasminogen activator after exposure to the endothelial cultures to B. bacilliformis extracts. Our results indicate that B. bacilliformis possess an activity that stimulates endothelial cell proliferation up to three times that of control. The factor(s) is specific for endothelial cells, heat sensitive, larger than 12 to 14 kd, not enhanced by heparin, has no affinity for heparin, and is precipitated by 45% ammonium sulfate. In addition, the B. bacilliformis extracts stimulate production of t-PA antigen in a concentration-dependent fashion. This activity is also heat sensitive and not lost after dialysis (12 to 14 kd). B. bacilliformis extracts, however, do not increase the production of plasminogen activator inhibitor. It was also determined that B. bacilliformis extracts stimulate the formation of new blood vessels in an in vivo model for angiogenesis. These results describe a bacterial factor(s) that stimulates two important steps in the development of new blood vessels in vitro, as well as the formation of new blood vessels in vivo. Determining the mechanism of action, combined with a complete characterization of this factor(s), may help in understanding the pathogenesis not only of the Verruga and angiogenesis in general but also the recently described Cat-Scratch-associated epithelioid hemangiomas in patients with AIDS and Kaposi sarcoma.
巴尔通体病是一种由运动性细胞内细菌引起的双相性疾病，在其组织阶段会产生特征性的皮肤疹（秘鲁疣），这是由明显的内皮细胞增殖所致。细菌存在于间质以及内皮细胞的细胞质内（罗查 - 利马包涵体）。本研究的目的是确定杆状巴尔通体是否产生某种物质，该物质可能是导致秘鲁疣中所见血管增殖的原因。这是在体外系统中使用人内皮细胞进行评估的，在将内皮细胞培养物暴露于杆状巴尔通体提取物后，测量其增殖情况以及组织型纤溶酶原激活物的产生。我们的结果表明，杆状巴尔通体具有一种活性，可刺激内皮细胞增殖，其增殖程度高达对照的三倍。该因子对内皮细胞具有特异性，对热敏感大小大于12至14kd，不受肝素增强，对肝素无亲和力，可被45%硫酸铵沉淀。此外，杆状巴尔通体提取物以浓度依赖的方式刺激t - PA抗原的产生。这种活性也对热敏感，透析后（12至14kd）不会丧失。然而，杆状巴尔通体提取物不会增加纤溶酶原激活物抑制剂的产生。还确定杆状巴尔通体提取物在体内血管生成模型中刺激新血管的形成。这些结果描述了一种细菌因子，它在体外刺激新血管发育的两个重要步骤，以及在体内刺激新血管的形成。确定其作用机制，并结合对该因子的全面表征，不仅可能有助于理解秘鲁疣和一般血管生成的发病机制，还可能有助于理解最近描述的艾滋病患者和卡波西肉瘤患者中与猫抓相关的上皮样血管瘤的发病机制。
