Young S K, Worthen G S, Haslett C, Tonnesen M G, Henson P M
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Am J Respir Cell Mol Biol. 1990 Jun;2(6):523-32. doi: 10.1165/ajrcmb/2.6.523.
Chemotactic peptides in the circulation stimulate neutrophils to become sequestered in the pulmonary vasculature, and low concentrations of bacterial lipopolysaccharide (LPS) enhance and prolong this effect. This interaction of neutrophils with the vascular endothelium is thought to involve, in part, the increase in adhesiveness induced in neutrophils by such stimuli. In this study, the binding of albumin-coated latex beads to neutrophils was used to determine whether the enhancement seen with LPS results from an increase in the number of adhesive cells, from the enhancement of the adhesiveness of individual neutrophils, or both. Chemotactic peptides alone and LPS alone induced an increase both in the adhesive population and in the number of beads bound per individual neutrophil. The number of beads bound per cell increased over a very wide range of stimulus concentrations, showing that the degree of adhesiveness of an individual cell in the population varies over a considerable range. Trace concentrations of LPS (10 ng/ml or less), i.e., levels close to those measurable in vivo, had little effect on the proportion of neutrophils that were stimulated by chemotactic factor to become adhesive but did significantly enhance the number of beads bound to each individual neutrophil. The enhancement may require the presence of the CD11/18 glycoprotein complex, but was not further upregulated by LPS. No evidence could be obtained to suggest that the effect of LPS involved release of tumor necrosis factor (TNF) from the numbers of monocytes in the preparation, and the observations are consistent with a direct effect of LPS on the neutrophils. It is suggested that this increase in adhesive sites on the cell could explain the persistence of the sequestration of neutrophils in the microvasculature seen in the presence of both chemoattractants and LPS by enhancing the "strength" of the adhesion to endothelial cells. The increased adhesion may also set the stage for enhanced endothelial injury.
循环中的趋化肽刺激中性粒细胞在肺血管系统中滞留，低浓度的细菌脂多糖（LPS）可增强并延长这种作用。中性粒细胞与血管内皮的这种相互作用被认为部分涉及此类刺激诱导中性粒细胞黏附性增加。在本研究中，使用白蛋白包被的乳胶珠与中性粒细胞的结合来确定LPS所见的增强作用是源于黏附细胞数量的增加、单个中性粒细胞黏附性的增强，还是两者兼有。单独的趋化肽和单独的LPS均可诱导黏附细胞群体增加以及单个中性粒细胞结合的珠粒数量增加。在非常广泛的刺激浓度范围内，每个细胞结合的珠粒数量都增加了，这表明群体中单个细胞的黏附程度在相当大的范围内变化。痕量浓度的LPS（10 ng/ml或更低），即接近体内可测量水平，对趋化因子刺激而变得黏附的中性粒细胞比例影响很小，但确实显著增加了每个单个中性粒细胞结合的珠粒数量。这种增强可能需要CD11/18糖蛋白复合物的存在，但不会被LPS进一步上调。没有证据表明LPS的作用涉及制剂中单核细胞释放肿瘤坏死因子（TNF），并且这些观察结果与LPS对中性粒细胞的直接作用一致。有人提出，细胞上黏附位点的这种增加可以解释在趋化剂和LPS同时存在的情况下，中性粒细胞在微血管系统中滞留的持续性，这是通过增强与内皮细胞黏附的“强度”来实现的。增加的黏附也可能为增强的内皮损伤奠定基础。
