Bristol-Myers Squibb Pharmaceutical Research Institute 100 Forest Avenue Buffalo NY 14213 USA.
Mediators Inflamm. 1994;3(6):459-63. doi: 10.1155/S0962935194000657.
The anti-inflammatory effect of a small molecular weight antagonist of P- and E-selectin-dependent cell adhesion was examined. The glycolipid sulphatide was shown to block the adherence of thrombin-activated rat platelets to HL-60 cells. This interaction is known to be dependent on P-selectin. The rat dermal reverse passive Arthus reaction was used to assess the effect of sulphatide on a neutrophil dependent inflammatory response. Sulphatide dosedependently blocked both the vascular permeability increase and cell infiltration after intraperitoneal administration. These results show that a small molecular weight compound which blocks P- and E-selectin dependent adhesion in vitro can effectively block the inflammation due to immune complex deposition. A compound with this type of profile may have therapeutic potential in the treatment of immune complex mediated diseases.
研究了一种 P 选择素和 E 选择素依赖性细胞黏附的小分子拮抗剂的抗炎作用。糖脂硫酸酯已被证明可阻止凝血酶激活的大鼠血小板与 HL-60 细胞的黏附。已知这种相互作用依赖于 P 选择素。使用大鼠皮肤反向被动 Arthus 反应来评估硫酸酯对中性粒细胞依赖性炎症反应的影响。硫酸酯剂量依赖性地阻断了腹腔内给药后血管通透性增加和细胞浸润。这些结果表明,一种在体外阻断 P 选择素和 E 选择素依赖性黏附的小分子化合物可以有效地阻断免疫复合物沉积引起的炎症。具有这种类型特征的化合物可能具有治疗免疫复合物介导疾病的潜力。