Lawrence M B, Berg E L, Butcher E C, Springer T A
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Eur J Immunol. 1995 Apr;25(4):1025-31. doi: 10.1002/eji.1830250425.
We studied leukocyte interactions in shear flow with peripheral lymph node addressin (PNAd), a mixture of glycoproteins expressed on high endothelial venules (HEV) that is required for lymphocyte homing and has been shown to contain a ligand for L-selectin. T lymphocytes and neutrophils tether and roll on plastic-immobilized PNAd and E-selectin at 1.8 dyn/cm2 wall shear stress, but fail to interact with immobilized ICAM-1, a ligand for LFA-1 and Mac-1, at the same flow rate. Cells roll faster on PNAd than on P-selectin or E-selectin. L-selectin mAb inhibit T lymphocyte and neutrophil tethering to PNAd, but do not inhibit T lymphocyte tethering to purified E-selectin. If allowed to interact with ICAM-1 under static conditions, phorbol ester-treated T lymphocytes, but not resting T lymphocytes, are able to form stationary adhesions that withstand the detachment force generated by 36 dyn/cm2 wall shear stress. In contrast, a wall shear stress of 7.3 dyn/cm2 detaches 50% of resting T lymphocytes bound to PNAd. Incubating T lymphocytes on PNAd and ICAM-1 does not result in adhesion strengthening, suggesting that adhesion through PNAd by L-selectin does not stimulate lymphocyte LFA-1 avidity for ICAM-1. Chemoattractant stimulation of neutrophils or phorbol ester stimulation of lymphoblasts rolling on coimmobilized PNAd and ICAM-1 results in rapid arrest and firm sticking, extending the model of sequential selectin-mediated rolling and subsequent integrin-mediated firm arrest to lymphocytes and ligands expressed on HEV.
我们研究了在剪切流中白细胞与外周淋巴结地址素（PNAd）的相互作用，PNAd是一种在高内皮微静脉（HEV）上表达的糖蛋白混合物，是淋巴细胞归巢所必需的，并且已被证明含有L-选择素的配体。T淋巴细胞和中性粒细胞在1.8达因/平方厘米的壁面剪应力下，能在固定于塑料上的PNAd和E-选择素上系留和滚动，但在相同流速下不能与固定的细胞间黏附分子-1（ICAM-1，LFA-1和Mac-1的配体）相互作用。细胞在PNAd上滚动的速度比在P-选择素或E-选择素上更快。L-选择素单克隆抗体抑制T淋巴细胞和中性粒细胞与PNAd的系留，但不抑制T淋巴细胞与纯化的E-选择素的系留。如果在静态条件下允许其与ICAM-1相互作用，佛波酯处理的T淋巴细胞（而非静止T淋巴细胞）能够形成抵抗36达因/平方厘米壁面剪应力产生的分离力的固定黏附。相比之下，7.3达因/平方厘米的壁面剪应力能使50%与PNAd结合的静止T淋巴细胞分离。在PNAd和ICAM-1上孵育T淋巴细胞不会导致黏附增强，这表明L-选择素通过PNAd的黏附不会刺激淋巴细胞LFA-1对ICAM-1的亲和力。对在共同固定的PNAd和ICAM-1上滚动的中性粒细胞进行趋化因子刺激或对淋巴母细胞进行佛波酯刺激会导致快速停滞和牢固黏附，将顺序选择素介导的滚动以及随后整合素介导的牢固停滞的模型扩展到淋巴细胞以及HEV上表达的配体。
