Finn A, Strobel S, Levin M, Klein N
Department of Paediatrics, University of Sheffield, Children's Hospital, England.
Ann N Y Acad Sci. 1994 May 28;725:173-82. doi: 10.1111/j.1749-6632.1994.tb39799.x.
The injury to vascular endothelium seen in severe bacterial infection may be mediated by neutrophil-derived enzymes. Neutrophil adhesion to endothelium, a prerequisite for this process, is mediated sequentially by the leukocyte adhesion molecules L-selectin and the beta 2 integrins, including CD11b/CD18. We have explored the relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury, as assessed in vitro by changes to HS and FN matrices that colocalize. Endothelial prestimulation with LPS (endotoxin) caused an increase in adherence and an inversely proportional disruption in the HS matrix; disruption of the FN matrix only occurred on the further addition of fMLP. Although maximal changes in these matrices were associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. CD11b/CD18 expression was similar in both adherent and nonadherent neutrophils, while L-selectin was shed in association with adherence in the absence of other stimuli. These changes in expression were thus independently regulated. This model may provide further insights into the interrelationship between neutrophil adhesion and activation and endothelial damage in infection with gram-negative bacteria.
在严重细菌感染中所见的血管内皮损伤可能由中性粒细胞衍生的酶介导。中性粒细胞与内皮的黏附是这一过程的前提条件，依次由白细胞黏附分子L-选择素和β2整合素（包括CD11b/CD18）介导。我们探讨了这些分子的表达、中性粒细胞黏附、内皮激活以及随之而来的内皮损伤之间的关系，这些关系通过共定位的硫酸乙酰肝素（HS）和纤连蛋白（FN）基质的变化在体外进行评估。用脂多糖（内毒素）对内皮进行预刺激会导致黏附增加以及HS基质中呈反比的破坏；仅在进一步添加fMLP时FN基质才会发生破坏。尽管这些基质中的最大变化与中性粒细胞CD11b/CD18升高和L-选择素表达降低相关，但这些变化并不能决定内皮损伤的性质或程度。黏附的和未黏附的中性粒细胞中CD11b/CD18表达相似，而在没有其他刺激的情况下，L-选择素会随着黏附而脱落。因此，这些表达变化是独立调节的。该模型可能会为革兰氏阴性菌感染中中性粒细胞黏附与激活以及内皮损伤之间的相互关系提供进一步的见解。
