Mulligan M S, Warner R L, Lowe J B, Smith P L, Suzuki Y, Miyasaka M, Yamaguchi S, Ohta Y, Tsukada Y, Kiso M, Hasegawa A, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Int Immunol. 1998 May;10(5):569-75. doi: 10.1093/intimm/10.5.569.
There is accumulating evidence that sulfated lipids, sulfated oligosaccharides and other sulfated compounds are reactive with selectins in a manner that interferes with selectin interactions with their natural ligands. In the report we describe the ability of sulfated lipids (sulfatides and gangliosides) and multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig to neutrophils. The in vivo ability of these compounds to block lung injury in rats following i.v. infusion of purified cobra venom factor (CVF), which induces injury that is L- and P-selectin dependent, was also determined as well as effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There was a significant correlation between the ability of sulfated lipids and sialyl compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to protect against P-selectin-dependent acute lung injury induced by CVF. The biological effects of these sulfated compounds were also associated with diminished accumulation of neutrophils. The protective effects of these compounds may be linked to their ability to interfere with P-selectin binding to counter-receptors on neutrophils.
越来越多的证据表明，硫酸化脂质、硫酸化寡糖和其他硫酸化化合物能够与选择素发生反应，从而干扰选择素与其天然配体的相互作用。在本报告中，我们描述了硫酸化脂质（硫苷脂和神经节苷脂）以及硫酸化唾液酸的多聚体形式阻断P-选择素和E-选择素免疫球蛋白与中性粒细胞结合的能力。还测定了这些化合物在静脉注射纯化的眼镜蛇毒因子（CVF）后对大鼠肺损伤的体内阻断能力，CVF诱导的损伤是L-选择素和P-选择素依赖性的，同时也测定了对中性粒细胞募集的影响，通过肺髓过氧化物酶进行测量。硫酸化脂质和唾液酸化合物在体外干扰P-选择素免疫球蛋白与中性粒细胞结合以及预防CVF诱导的P-选择素依赖性急性肺损伤的能力之间存在显著相关性。这些硫酸化化合物的生物学效应也与中性粒细胞的积累减少有关。这些化合物的保护作用可能与其干扰P-选择素与中性粒细胞上反受体结合的能力有关。
