Kubo H, Doyle N A, Graham L, Bhagwan S D, Quinlan W M, Doerschuk C M
Physiology Program, Harvard School of Public Health, Boston, Massachusetts, USA.
Am J Respir Crit Care Med. 1999 Jan;159(1):267-74. doi: 10.1164/ajrccm.159.1.9709011.
Infusion of complement fragments induces rapid sequestration of neutrophils within pulmonary capillaries. This study examined the mechanisms through which this sequestration occurs, as well as the effect of complement fragments on the expression of L-selectin and CD11/CD18 using ultrastructural immunohistochemistry. Studies using anti-P-selectin antibodies, fucoidin, L-selectin-depleted neutrophils, and anti-CD18 antibodies showed that selectins and CD18 were not required for neutrophil sequestration. However, maintaining the sequestered neutrophils within the pulmonary capillaries required both L-selectin and CD11/CD18. Neutrophils in the pulmonary capillaries of rabbits given complement fragments expressed 72% less L-selectin and 98% more CD11/CD18 than did those in rabbits given saline. Shedding of L-selectin occurred preferentially from the microvillar processes of the plasma membrane rather than from the flat intervening regions. About 28% of L-selectin still remained on intracapillary neutrophil membranes after 15 min and was likely available for binding. Shedding of L-selectin appeared slower in vivo than in vitro. These studies indicate that neutrophil sequestration induced by complement fragments requires at least two sequential steps, one that does not require recognized adhesion molecules followed by a second that requires L-selectin and CD11/ CD18.
补体片段的输注可诱导中性粒细胞在肺毛细血管内迅速滞留。本研究通过超微结构免疫组织化学检查了这种滞留发生的机制，以及补体片段对L-选择素和CD11/CD18表达的影响。使用抗P-选择素抗体、岩藻依聚糖、L-选择素缺失的中性粒细胞和抗CD18抗体的研究表明，中性粒细胞滞留不需要选择素和CD18。然而，将滞留的中性粒细胞维持在肺毛细血管内需要L-选择素和CD11/CD18。给予补体片段的家兔肺毛细血管中的中性粒细胞表达的L-选择素比给予生理盐水的家兔少72%，而CD11/CD18多98%。L-选择素的脱落优先发生在质膜的微绒毛突起处，而不是在平坦的中间区域。15分钟后，约28%的L-选择素仍保留在毛细血管内中性粒细胞膜上，可能可供结合。L-选择素在体内的脱落似乎比在体外慢。这些研究表明，补体片段诱导的中性粒细胞滞留至少需要两个连续步骤，一个不需要公认的粘附分子，另一个需要L-选择素和CD11/CD18。
