Doyle N A, Bhagwan S D, Meek B B, Kutkoski G J, Steeber D A, Tedder T F, Doerschuk C M
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
J Clin Invest. 1997 Feb 1;99(3):526-33. doi: 10.1172/JCI119189.
These studies tested the hypothesis that L-selectin plays a role in neutrophil traffic in the lungs, particularly in neutrophil margination, sequestration, and emigration, using L-selectin-deficient mice. No defect in neutrophil margination within either capillaries or arterioles and venules was observed in uninflamed lungs of L-selectin-deficient mice. The initial rapid sequestration of neutrophils within the pulmonary capillaries 1 min after intravascular injection of complement fragments was not prevented. In contrast, L-selectin did contribute to the prolonged neutrophil sequestration (> or = 5 min). Interestingly, neutrophil accumulation within noncapillary microvessels required L-selectin at both 1 and 5 min after complement injection. During bacterial pneumonias, L-selectin played a role in neutrophil accumulation within noncapillary microvessels in response to either Escherichia coli or Streptococcus pneumoniae and within capillaries in response to E. coli but not S. pneumoniae. However, L-selectin was not required for emigration of neutrophils or edema in response to either organism. These studies demonstrate a role for L-selectin in the prolonged sequestration of neutrophils in response to intravascular complement fragments, in the intracapillary accumulation of neutrophils during E. coli-induced pneumonia, and in the accumulation of neutrophils within noncapillary microvessels when induced by either intravascular complement fragments or
这些研究利用L-选择素缺陷小鼠,检验了L-选择素在肺部中性粒细胞运输中发挥作用的假说,特别是在中性粒细胞靠边、滞留和游出方面。在L-选择素缺陷小鼠的未发炎肺中,未观察到毛细血管或小动脉及小静脉内中性粒细胞靠边存在缺陷。血管内注射补体片段1分钟后,肺部毛细血管内中性粒细胞最初的快速滞留并未受到阻止。相比之下,L-选择素确实促成了中性粒细胞的长时间滞留(≥5分钟)。有趣的是,补体注射后1分钟和5分钟时,非毛细血管微血管内的中性粒细胞积聚均需要L-选择素。在细菌性肺炎期间,L-选择素在对大肠杆菌或肺炎链球菌的反应中,在非毛细血管微血管内的中性粒细胞积聚中发挥作用,而在对大肠杆菌而非肺炎链球菌的反应中,在毛细血管内的中性粒细胞积聚中发挥作用。然而,无论是哪种病原体引起的中性粒细胞游出或水肿,均不需要L-选择素。这些研究证明,L-选择素在对血管内补体片段的反应中,在中性粒细胞的长时间滞留中发挥作用;在大肠杆菌诱导的肺炎期间,在中性粒细胞的毛细血管内积聚中发挥作用;以及在由血管内补体片段或……诱导时,在非毛细血管微血管内的中性粒细胞积聚中发挥作用。