Bajaj M S, Kuppuswamy M N, Saito H, Spitzer S G, Bajaj S P
Department of Medicine, Saint Louis University School of Medicine, MO 63104.
Proc Natl Acad Sci U S A. 1990 Nov;87(22):8869-73. doi: 10.1073/pnas.87.22.8869.
Human plasma contains a factor Xa-dependent inhibitor of tissue factor/factor VIIa complex termed lipoprotein-associated coagulation inhibitor (LACI). The present study examines the site(s) of LACI synthesis. In this study, cultured hepatocytes isolated from normal human liver were found to be essentially negative in LACI mRNA as revealed by Northern blot analysis using a full-length LACI cDNA as probe. The conditioned media from these cultures were also essentially negative for LACI activity. Similarly, poly(A)+ RNA obtained from normal human liver did not contain detectable LACI mRNA. In contrast, cultured human umbilical vein endothelial cells and human lung tissue (rich in endothelium) both contained abundant amounts of LACI mRNA. Moreover, erythrocyte lysates and culture media from normal monocytes, lymphocytes, or neutrophils did not contain measurable LACI activity; these cells were also negative for LACI mRNA. Platelets, however, contained LACI activity. The likely source of platelet LACI is the megakaryocyte cell since a megakaryocyte cell line (MEG-01) was found to contain LACI mRNA and to secrete small amounts of LACI activity. Additionally, human vascular smooth muscle cells and lung fibroblasts were also found to synthesize only small amounts of LACI. From these observations, we conclude that normal liver does not synthesize LACI and that endothelium is the principal source of plasma LACI. The undegraded LACI synthesized by endothelial cells had a molecular weight of approximately 41,000.
人血浆中含有一种组织因子/因子VIIa复合物的Xa因子依赖性抑制剂，称为脂蛋白相关凝血抑制剂（LACI）。本研究检测了LACI的合成部位。在本研究中，使用全长LACI cDNA作为探针进行Northern印迹分析发现，从正常人肝脏分离的培养肝细胞的LACI mRNA基本呈阴性。这些培养物的条件培养基的LACI活性也基本为阴性。同样，从正常人肝脏获得的poly(A)+ RNA也未检测到LACI mRNA。相比之下，培养的人脐静脉内皮细胞和人肺组织（富含内皮）均含有大量的LACI mRNA。此外，正常单核细胞、淋巴细胞或中性粒细胞的红细胞裂解物和培养基中均未检测到可测量的LACI活性；这些细胞的LACI mRNA也呈阴性。然而，血小板含有LACI活性。血小板LACI的可能来源是巨核细胞，因为发现一种巨核细胞系（MEG-01）含有LACI mRNA并分泌少量LACI活性。此外，还发现人血管平滑肌细胞和肺成纤维细胞仅合成少量LACI。根据这些观察结果，我们得出结论，正常肝脏不合成LACI，内皮是血浆LACI的主要来源。内皮细胞合成的未降解LACI的分子量约为41,000。
