Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion
Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion
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DOI：
10.1152/ajpheart.1998.274.5.h1785
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发表时间：
1998-05-01
影响因子：
4.8
通讯作者：
Ley, K
中科院分区：
文献类型：
--
作者：
Jung, U;Ramos, CL;Ley, K
目前尚不清楚l -选择素介导的滚动是否能独立于P-和e -选择素促进体内白细胞粘附。我们使用活体显微镜对E-和P-选择素双突变小鼠（E-/P-）进行肿瘤坏死因子- α刺激6-8小时，以研究l -选择素依赖性滚动在肌小静脉中的重要性。E-/P-小鼠的滚动白细胞通量为9 +/- 2个细胞/min，而野生型（WT）小鼠为77 +/- 17个细胞/min。l -选择素单克隆抗体MEL-14预处理显著降低E-/P-(89%)和WT小鼠（79%）的滚动。E-/P-小鼠的l -选择依赖滚动导致白细胞粘附，与WT小鼠相似。MEL-14预处理可使E-/P-小鼠白细胞粘附降低50%。在WT和E-/P-小鼠中，大多数（约80%）血管内白细胞是中性粒细胞。我们得出结论，l -选择素可以介导滚动，导致足够的白细胞募集，以解释E-/P-小鼠在后期出现的强烈炎症反应。
It has not been determined whether L-selectin-mediated rolling can promote leukocyte adhesion in vivo independent of P- and E-selectin. We used intravital microscopy of E- and P-selectin double-mutant mice (E-/P-) stimulated with tumor necrosis factor-alpha for 6-8 h to investigate the importance of L-selectin-dependent rolling in cremaster muscle venules. Rolling leukocyte flux in E-/P- mice was 9 +/- 2 cells/min compared with 77 +/- 17 cells/min in wild-type (WT) mice. Pretreatment with the L-selectin monoclonal antibody MEL-14 significantly reduced rolling in both E-/P- (by 89%) and WT mice (by 79%). L-selectin-dependent rolling in E-/P- mice resulted in leukocyte adhesion comparable to that seen in WT mice. MEL-14 pretreatment of E-/P- mice reduced leukocyte adhesion by 50%. The majority (similar to 80%) of intravascular leukocytes in both WT and E-/P- mice were neutrophils. We conclude that L-selectin can mediate rolling that results in sufficient leukocyte recruitment to account for the robust inflammatory response seen in E-/P- mice at later times.