Matera Giovanni, Liberto Maria Carla, Quirino Angela, Barreca Giorgio Settimo, Lamberti Angelo Giuseppe, Iannone Michelangelo, Mancuso Eliana, Palma Ernesto, Cufari Francesco Antonio, Rotiroti Domenicantonio, Focà Alfredo
Institute of Microbiology, Department of Medical Sciences, Faculty of Medicine, University of Catanzaro, Via T. Campanella 115, I-88100, Catanzaro, Italy.
Int Immunopharmacol. 2003 Jun;3(6):853-64. doi: 10.1016/S1567-5769(03)00059-6.
Bartonella quintana, an emerging gram-negative pathogen, may cause trench fever, endocarditis, cerebral abscess and bacillary angiomatosis usually with the absence of septic shock in humans. B. quintana lipopolysaccharide (LPS), a deep rough endotoxin with strong reactivity in the limulus amebocyte lysate (LAL)-assay, was studied in human whole blood and in a rat model. A significant (P<0.05) increase of interleukin-8 (IL-8) concentration, comparable to the level induced by enterobacterial LPS, was stimulated in the human whole blood by B. quintana LPS. Isolated human neutrophils delayed their apoptotic behavior in the presence of B. quintana LPS. In the rat, B. quintana LPS induced a significant (P<0.001) increase in white blood cell count, both 30 and 60 min after intravenous injection. Such leukocytosis was inhibited by pretreatment with prazosin, an alpha-adrenergic antagonist. B. quintana LPS did not significantly change heart rate (HR), hematocrit (HCT) and platelet count in the above reported in vivo model, and regarding mean blood pressure (MAP) only a very early (5 min after LPS) and mild (yet significant) hypotension was observed. In contrast, a long-lasting decrease of MAP was found in Salmonella minnesota R595 LPS-treated animals. Blood TNFalpha levels did not change significantly from the baseline in rats injected with either saline or with B. quintana LPS, on the contrary S. minnesota R595 LPS-injected animals showed substantial increase of TNFalpha levels up to 2924 pg/ml at 60 min after LPS injection. B. quintana LPS as well as Salmonella LPS-injected rats exhibited an increase of the blood levels of GRO/CINC-1, particularly at 240 min after LPS administration. Apical part of rat gut villi showed several TUNEL-positive cells in tissue sections from B. quintana LPS-treated animals. Taken together, our data demonstrates that B. quintana LPS is able to selectively stimulate some inflammatory mediators. B. quintana LPS-induced leukocytosis appears mediated by an alpha-adrenergic receptor. The delayed apoptotic process of leukocytes and the chemokine increase may explain the apoptotic cells found in the rat gut and the inflammatory reactions in some human Bartonella diseases. This peculiar inflammatory pattern induced by B. quintana LPS, may partially account for the lack of severe septic shock, observed in human B. quintana infections.
五日热巴尔通体是一种新出现的革兰氏阴性病原体，可引起战壕热、心内膜炎、脑脓肿和杆菌性血管瘤病，在人类中通常不会出现感染性休克。对五日热巴尔通体脂多糖（LPS）进行了人体全血和大鼠模型研究，该脂多糖是一种在鲎试剂检测中具有强反应性的深粗糙内毒素。五日热巴尔通体LPS可刺激人体全血中白细胞介素-8（IL-8）浓度显著升高（P<0.05），升高水平与肠道细菌LPS诱导的水平相当。在五日热巴尔通体LPS存在的情况下，分离出的人体中性粒细胞延迟了其凋亡行为。在大鼠中，静脉注射五日热巴尔通体LPS后30分钟和60分钟，白细胞计数显著升高（P<0.001）。这种白细胞增多症可被α-肾上腺素能拮抗剂哌唑嗪预处理所抑制。在上述体内模型中，五日热巴尔通体LPS并未显著改变心率（HR）、血细胞比容（HCT）和血小板计数，关于平均血压（MAP），仅观察到非常早期（LPS注射后5分钟）和轻度（但显著）的低血压。相比之下，在注射明尼苏达沙门氏菌R595 LPS的动物中发现MAP持续下降。注射生理盐水或五日热巴尔通体LPS的大鼠血液TNFα水平与基线相比无显著变化，相反，注射明尼苏达沙门氏菌R595 LPS的动物在LPS注射后60分钟时TNFα水平大幅升高至2924 pg/ml。注射五日热巴尔通体LPS以及沙门氏菌LPS的大鼠血液中GRO/CINC-1水平均升高，尤其是在LPS给药后240分钟时。在五日热巴尔通体LPS处理动物的组织切片中，大鼠肠绒毛顶端部分显示出几个TUNEL阳性细胞。综上所述，我们的数据表明，五日热巴尔通体LPS能够选择性地刺激一些炎症介质。五日热巴尔通体LPS诱导的白细胞增多症似乎是由α-肾上腺素能受体介导的。白细胞凋亡过程延迟和趋化因子增加可能解释了在大鼠肠道中发现的凋亡细胞以及人类一些巴尔通体疾病中的炎症反应。五日热巴尔通体LPS诱导的这种特殊炎症模式可能部分解释了在人类五日热巴尔通体感染中观察到的严重感染性休克的缺乏。
