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全血介导的内皮通透性和黏附分子表达:关于细菌和抗生素作用的模型研究

Whole blood-mediated endothelial permeability and adhesion molecule expression: a model study into the effects of bacteria and antibiotics.

作者信息

Nooteboom Arjan, van der Linden Cees J, Hendriks Thijs

机构信息

Department of Surgery, University Medical Centre Nijmegen, PO box 9101, 6500 HB Nijmegen.

出版信息

J Antimicrob Chemother. 2005 Feb;55(2):150-6. doi: 10.1093/jac/dkh526. Epub 2005 Jan 13.

Abstract

AIM

To investigate whether the inflammatory response of cultured endothelial cells, as induced by conditioned plasma, depends on the bacterial species or type of antibiotic used for incubation with whole blood.

MATERIALS AND METHODS

Blood from healthy volunteers was stimulated ex vivo with different microorganisms, and with bacteria killed with different antibiotics. The resultant plasmas were incubated on monolayers of cultured human endothelial cells, followed by measurement of their permeability to albumin and expression of E-selectin and intercellular adhesion molecule-1.

RESULTS

Incubation of Escherichia coli in blood yielded plasmas that induced a marked increase in endothelial permeability and E-selectin expression. The response to Bacteroides fragilis or Enterococcus faecalis was generally weaker. Similar effects were observed after incubation of whole blood with lipopolysaccharide (LPS). Much of the permeability and adhesion molecule response to E. coli remained after removal of intact microorganisms from the culture. Whereas antibiotic treatment of E. coli with imipenem or cefuroxime resulted in a divergent production of tumour necrosis factor-alpha (TNF-alpha) in blood, no significant differences between these treatments were observed with respect to the plasma-induced endothelial response.

CONCLUSION

Bacteria differ in their capacity to generate a whole blood-mediated increase of endothelial permeability and adhesion molecule expression; this response depends, at least in part, on the presence of soluble bacterial components, such as LPS. Whereas treatment with various antibiotics may generate varying amounts of TNF-alpha, these differences are not translated into differences in endothelial permeability or adhesion molecule expression.

摘要

目的

研究条件血浆诱导的培养内皮细胞炎症反应是否取决于与全血一起孵育所用的细菌种类或抗生素类型。

材料与方法

用不同微生物以及用不同抗生素杀死的细菌对健康志愿者的血液进行离体刺激。将所得血浆在培养的人内皮细胞单层上孵育,随后测量其对白蛋白的通透性以及E-选择素和细胞间黏附分子-1的表达。

结果

血液中孵育大肠杆菌产生的血浆可诱导内皮通透性和E-选择素表达显著增加。对脆弱拟杆菌或粪肠球菌的反应通常较弱。用脂多糖(LPS)孵育全血后也观察到类似效果。从培养物中去除完整微生物后,对大肠杆菌的通透性和黏附分子反应仍大部分存在。用亚胺培南或头孢呋辛对大肠杆菌进行抗生素处理会导致血液中肿瘤坏死因子-α(TNF-α)产生不同,但在血浆诱导的内皮反应方面,这些处理之间未观察到显著差异。

结论

细菌在引发全血介导的内皮通透性增加和黏附分子表达方面的能力不同;这种反应至少部分取决于可溶性细菌成分(如LPS)的存在。虽然用各种抗生素治疗可能会产生不同量的TNF-α,但这些差异并未转化为内皮通透性或黏附分子表达的差异。

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