Macrophages express osteopontin during repair of myocardial necrosis.
Macrophages express osteopontin during repair of myocardial necrosis.
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发表时间：
1994-12
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通讯作者：
C. Murry;C. Giachelli;S. Schwartz;R. Vracko
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作者：
C. Murry;C. Giachelli;S. Schwartz;R. Vracko
骨桥蛋白是一种分泌性糖蛋白，涉及多种功能，包括细胞粘附和迁移。由于这些功能可能在组织对损伤的反应中具有普遍重要性，因此我们检查了实验性心脏损伤和人心肌梗塞后骨桥蛋白的表达。通过经膈冻融损伤大鼠心脏，并在损伤后 1 至 28 天进行检查。通过免疫细胞化学、蛋白质印迹和原位杂交，正常心肌中不存在骨桥蛋白。损伤后第1天和第2天，浸润坏死心肌的巨噬细胞高水平表达骨桥蛋白mRNA和蛋白。然而，巨噬细胞标记物 ED1 的双重标记表明，只有一部分巨噬细胞表达骨桥蛋白。蛋白质印迹分析显示，受损心肌中存在一条 66-kd 条带，而对照组织中则没有该条带。尽管巨噬细胞在随后的肉芽反应和疤痕组织形成中仍然丰富，但骨桥蛋白的表达在第4天减少，并在损伤后1周和4周显着下调，只有极少数细胞表达信息或蛋白质。在患有 8 天心肌梗死的人心脏中，坏死组织和肉芽组织内的巨噬细胞中存在丰富的骨桥蛋白 mRNA 和蛋白表达。在实验过程中受伤的浸润肺、皮肤和骨骼肌的巨噬细胞子集中也观察到骨桥蛋白的瞬时表达，表明这种反应不仅限于心脏。因此，巨噬细胞合成骨桥蛋白似乎是对组织损伤反应的普遍反应。尽管巨噬细胞持续存在于这些病变中，但骨桥蛋白随着愈合的进行而急剧下调。这些结果提供了第一个证据，表明骨桥蛋白在组织损伤后的愈合中可能很重要，可能在细胞粘附、趋化性和/或吞噬作用中。
Osteopontin is a secreted glycoprotein implicated in a variety of functions, including cell adhesion and migration. Because these functions may be of general importance in the response of tissue to injury, we examined osteopontin expression after experimental cardiac injury and human myocardial infarction. Rat hearts were injured by transdiaphragmatic freeze-thaw and examined from 1 to 28 days after injury. Osteopontin was absent from normal myocardium by immunocytochemistry, Western blotting, and in situ hybridization. On days 1 and 2 after injury, osteopontin mRNA and protein were expressed at high levels by macrophages infiltrating necrotic myocardium. Double labeling with the macrophage marker ED1, however, demonstrated that only a subset of macrophages expressed osteopontin. Western blot analysis showed a single 66-kd band in injured myocardium that was absent from control tissue. Although macrophages remained abundant in the ensuing granulation response and scar tissue formation, the expression of osteopontin was diminished on day 4 and markedly downregulated at 1 and 4 weeks after injury, with only rare cells expressing the message or protein. In a human heart with an 8-day-old myocardial infarct, there was abundant expression of osteopontin mRNA and protein in macrophages within the necrotic and granulation tissue. Transient expression of osteopontin was also observed in a subset of macrophages infiltrating lung, skin, and skeletal muscle injured during the experiment, indicating the response was not limited to the heart. Thus, synthesis of osteopontin by macrophages appears to be a generalized response in the reaction to tissue injury. Although macrophages persist in these lesions, osteopontin is dramatically downregulated as healing proceeds. These results provide the first evidence that osteopontin may be important in healing after tissue injury, possibly in cellular adhesion, chemotaxis, and/or phagocytosis.