Shimada K, Ozawa T
Department of Medicine and Geriatrics, Kochi Medical School, Japan.
Heart Vessels. 1987;3(4):175-81. doi: 10.1007/BF02058308.
At the early stage of atherogenesis, circulating monocyte macrophages appear to adhere to the endothelial cell surface and migrate subendothelially to become foam cells. The mechanism of these macrophage-endothelial cell interactions was investigated. Adherent macrophages isolated from human blood were plated on [35S]O4-prelabeled extracellular matrix-coated dishes prepared from cultured porcine aortic endothelial cells. During incubation for 2-3 days at pH 7.4 either in the presence or absence of serum, macrophages solubilized the labeled extracellular matrix to a lower molecular weight component (Kav approximately equal to 0.5) than the materials (Kav = 0) released into the medium containing no cells. The degrading activity was not stored intracellularly but instead was found pericellularly, requiring continuous cell-matrix contact. Heparin (10 micrograms/ml) inhibited this degrading activity of macrophages. Degradation products were precipitated with cetylpyridinium chloride and were resistant to further digestion with alkali, pronase, or chondroitinase ABC, but were converted to further lower molecular weight fragments (Kav = 0.84) after nitrous acid digestion or heparitinase treatment. The intact glycosaminoglycan side chains determined by subjecting the extracellular matrix to cleavage with alkali or pronase were larger (Kav congruent to 0.20) than those of degradation products released by macrophages. These results suggest that the attachment and subsequent invasion of endothelial cells by monocyte macrophages may involve the production of extracellular-matrix heparan sulfate proteoglycan-degrading activity by these cells.
在动脉粥样硬化形成的早期阶段，循环中的单核细胞巨噬细胞似乎会黏附在内皮细胞表面，并在内皮下迁移，进而成为泡沫细胞。对这些巨噬细胞与内皮细胞相互作用的机制进行了研究。从人血液中分离出的黏附巨噬细胞被接种在由培养的猪主动脉内皮细胞制备的[35S]O4预标记的细胞外基质包被培养皿上。在pH 7.4条件下，无论有无血清，培养2至3天期间，巨噬细胞将标记的细胞外基质溶解为分子量比释放到无细胞培养基中的物质（Kav = 0）更低的成分（Kav约等于0.5）。降解活性并非储存在细胞内，而是在细胞周围被发现，需要细胞与基质持续接触。肝素（10微克/毫升）可抑制巨噬细胞的这种降解活性。降解产物用十六烷基氯化吡啶沉淀，对碱、链霉蛋白酶或软骨素酶ABC的进一步消化具有抗性，但在亚硝酸消化或硫酸乙酰肝素酶处理后会转化为分子量更低的片段（Kav = 0.84）。通过用碱或链霉蛋白酶裂解细胞外基质确定的完整糖胺聚糖侧链比巨噬细胞释放的降解产物的侧链更大（Kav约等于0.20）。这些结果表明，单核细胞巨噬细胞对内皮细胞的黏附及随后的侵袭可能涉及这些细胞产生的细胞外基质硫酸乙酰肝素蛋白聚糖降解活性。
