Tomasko M A, Chudwin D S
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
J Lab Clin Med. 1988 Aug;112(2):248-53.
Patients with sickle cell disease (SCD) have poorly defined abnormalities of their alternative complement pathway (ACP). We have previously shown chronic activation of the ACP in these patients. To determine the mechanism of this finding, we studied concentrations of the complement control proteins factors I and H in serum from patients with SCD and found no significant difference when they were compared with a control population. Because certain membrane surfaces promote ACP activation and changes occur in erythrocyte membrane phospholipid organization with sickling, we used a liposome model to determine whether ACP activation could be caused by abnormal phospholipid organization of sickle cells. Liposomes with the composition of the sickle cell outer leaflet, which is enriched in phosphatidylserine and phosphatidylethanolamine, activated the ACP significantly more than liposomes with normal outer leaflet phospholipid content. Similarly, liposomes with the composition of the erythrocyte inner membrane leaflet, containing large amounts of phosphatidylethanolamine and phosphatidylserine, activated the ACP more than liposomes with the phospholipid content of the outer leaflet. These findings suggest that phospholipid composition of membranes may play a role in their ability to promote ACP activation, and that changes in phospholipid organization in sickle cells may contribute to the chronic ACP activation observed in patients with SCD.
镰状细胞病（SCD）患者的替代补体途径（ACP）存在异常，但具体情况尚不明确。我们之前已经表明这些患者的ACP处于慢性激活状态。为了确定这一发现的机制，我们研究了SCD患者血清中补体调节蛋白I因子和H因子的浓度，发现与对照人群相比没有显著差异。由于某些膜表面会促进ACP激活，并且镰状化时红细胞膜磷脂组织会发生变化，我们使用脂质体模型来确定镰状细胞异常的磷脂组织是否会导致ACP激活。具有镰状细胞外叶组成的脂质体，其富含磷脂酰丝氨酸和磷脂酰乙醇胺，比具有正常外叶磷脂含量的脂质体更能显著激活ACP。同样，具有红细胞内膜叶组成的脂质体，含有大量的磷脂酰乙醇胺和磷脂酰丝氨酸，比具有外叶磷脂含量的脂质体更能激活ACP。这些发现表明膜的磷脂组成可能在其促进ACP激活的能力中发挥作用，并且镰状细胞中磷脂组织的变化可能导致SCD患者中观察到的慢性ACP激活。
