Davenpeck K L, Steeber D A, Tedder T F, Bochner B S
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Immunol. 1997 Aug 15;159(4):1977-86.
Endotoxin is a potent stimulus of leukocyte infiltration, but the adhesion-related mechanisms responsible for LPS-induced cell recruitment events in vivo remain poorly characterized. Utilizing intravital microscopy, we examined the role of P- and L-selectin in LPS-induced inflammation. We demonstrated that superfusion of rat mesentery with LPS resulted in significant increases in both leukocyte rolling and adherence, which were maintained for at least 2 h. Pretreatment with a P-selectin neutralizing mAb only partially inhibited LPS-induced leukocyte rolling, but completely inhibited LPS-induced leukocyte adherence throughout the 2-h observation period. Pretreatment with an L-selectin neutralizing mAb dramatically inhibited LPS-induced increases in leukocyte rolling, but unlike the P-selectin mAb did not inhibit leukocyte adhesion. Fucoidin, which blocks both P- and L-selectin function, completely inhibited LPS-induced leukocyte rolling and adhesion. Consistent with previous studies, leukocyte rolling velocities on P-selectin were observed to be far less than velocities observed for leukocytes rolling on L-selectin in vivo. These data suggest that P-selectin plays a role in LPS-induced rolling and is essential for LPS-induced leukocyte adherence, while L-selectin functions in LPS-induced rolling, but not in adhesion.
内毒素是白细胞浸润的强效刺激物，但体内负责脂多糖（LPS）诱导的细胞募集事件的黏附相关机制仍未得到充分表征。利用活体显微镜，我们研究了P-选择素和L-选择素在LPS诱导的炎症中的作用。我们证明，用LPS灌注大鼠肠系膜会导致白细胞滚动和黏附显著增加，并持续至少2小时。用P-选择素中和单克隆抗体预处理仅部分抑制LPS诱导的白细胞滚动，但在整个2小时观察期内完全抑制LPS诱导的白细胞黏附。用L-选择素中和单克隆抗体预处理显著抑制LPS诱导的白细胞滚动增加，但与P-选择素单克隆抗体不同的是，它不抑制白细胞黏附。岩藻依聚糖可阻断P-选择素和L-选择素的功能，完全抑制LPS诱导的白细胞滚动和黏附。与先前的研究一致，观察到白细胞在P-选择素上的滚动速度远低于体内白细胞在L-选择素上滚动的速度。这些数据表明，P-选择素在LPS诱导的滚动中起作用，并且对LPS诱导的白细胞黏附至关重要，而L-选择素在LPS诱导的滚动中起作用，但在黏附中不起作用。
