Worthen G S, Schwab B, Elson E L, Downey G P
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO.
Science. 1989 Jul 14;245(4914):183-6. doi: 10.1126/science.2749255.
The effect of peptide chemoattractants on neutrophil mechanical properties was studied to test the hypothesis that stimulated neutrophils (diameter, 8 micrometers) are retained in pulmonary capillaries (5.5 micrometers) as a result of a decreased ability of the cell to deform within the capillary in response to the hydrodynamic forces of the bloodstream. Increased neutrophil stiffness, actin assembly, and retention in both 5-micrometer pores and the pulmonary vasculature were seen in response to N-formyl-methionyl-leucyl-phenylalanine. These changes were abolished in cells that had been incubated with 2 micromolar cytochalasin D, an agent that disrupts cellular actin organization. A monoclonal antibody directed at the CD11-CD18 adhesive glycoprotein complex did not inhibit the increase in stiffness or retention in pores. These data suggest that neutrophil stiffening may be both necessary and sufficient for the retention that is observed. Hence, neutrophil sequestration in lung and other capillaries in the acute inflammatory process may be the result of increased stiffness stimulated by chemoattractants.
研究了肽趋化因子对中性粒细胞力学特性的影响，以验证以下假说：受刺激的中性粒细胞（直径8微米）因细胞在毛细血管内响应血流动力而变形的能力下降，从而滞留在肺毛细血管（5.5微米）中。响应N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸，观察到中性粒细胞硬度增加、肌动蛋白组装增加，以及在5微米孔隙和肺血管系统中的滞留增加。在用2微摩尔细胞松弛素D（一种破坏细胞肌动蛋白组织的试剂）孵育过的细胞中，这些变化消失了。一种针对CD11-CD18黏附糖蛋白复合物的单克隆抗体并未抑制硬度增加或在孔隙中的滞留。这些数据表明，中性粒细胞变硬可能对于所观察到的滞留既是必要的也是充分的。因此，急性炎症过程中肺和其他毛细血管中的中性粒细胞隔离可能是趋化因子刺激导致硬度增加的结果。
