Ridger V C, Wagner B E, Wallace W A, Hellewell P G
Cardiovascular Research Group, Division of Clinical Sciences, Northern General Hospital, University of Sheffield, Sheffield, United Kingdom.
J Immunol. 2001 Mar 1;166(5):3484-90. doi: 10.4049/jimmunol.166.5.3484.
Neutrophil migration to lung alveoli is a characteristic of lung diseases and is thought to occur primarily via capillaries rather than postcapillary venules. The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neutrophils present in bronchoalveolar lavage fluid was determined 4 h after intratracheal instillation of LPS (0.1-1 microg) or murine recombinant KC (CXC chemokine, 0.03-0.3 microg). Both stimuli produced a dose-related increase in neutrophil accumulation. Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse), significantly (p < 0.001) attenuated LPS (0.3 microg)- but not KC (0.3 microg)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HM beta 1-1 (0.02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 microg)- and KC (0.3 microg)-induced neutrophil migration. A second mAb to CD18 (GAME-46) and both F(ab')(2) and Fab of HM beta 1-1 produced similar results to those above, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement of neutrophils from the interstitium into alveoli. The effect of mAbs to CD49 (alpha integrin) subunits of CD29 was also examined. mAbs to CD49e and CD49f inhibited both responses, while anti-CD49b and CD49d significantly inhibited responses to KC only. These data suggest that CD29 plays a critical role in neutrophil migration in pulmonary inflammation and that CD49b and CD49d mediate CD18-independent neutrophil accumulation.
中性粒细胞向肺泡迁移是肺部疾病的一个特征，并且被认为主要通过毛细血管而非毛细血管后微静脉发生。在肺部炎症小鼠模型中，已对黏附分子CD18和CD29在这种迁移过程中的作用进行了研究。在气管内滴注脂多糖（0.1 - 1微克）或小鼠重组KC（CXC趋化因子，0.03 - 0.3微克）4小时后，测定支气管肺泡灌洗液中中性粒细胞的数量。两种刺激均使中性粒细胞积聚呈剂量相关增加。静脉注射抗小鼠CD18单克隆抗体2E6（0.5毫克/只小鼠）显著（p < 0.001）减弱脂多糖（0.3微克）诱导的中性粒细胞积聚，但对KC（0.3微克）诱导的中性粒细胞积聚无影响。抗小鼠CD29单克隆抗体HMβ1 - 1（0.02毫克/只小鼠）显著（p < 0.05）抑制脂多糖（0.3微克）和KC（0.3微克）诱导的中性粒细胞迁移。针对CD18的第二种单克隆抗体（GAME - 46）以及HMβ1 - 1的F(ab')(2)片段和Fab片段产生了与上述相似的结果，而同时给予单克隆抗体并未导致更强的抑制作用。电子显微镜研究表明，CD29参与中性粒细胞从间质向肺泡的移动。还检测了针对CD29的CD49（α整合素）亚基的单克隆抗体的作用。针对CD49e和CD49f的单克隆抗体抑制了两种反应，而抗CD49b和抗CD49d仅显著抑制对KC的反应。这些数据表明，CD29在肺部炎症中中性粒细胞迁移中起关键作用，并且CD49b和CD49d介导不依赖CD18的中性粒细胞积聚。
