Kreuzer J, Bader J, Jahn L, Hautmann M, Kübler W, Von Hodenberg E
Department of Cardiology, University Hospital, Heidelberg, F.R.G.
Atherosclerosis. 1991 Oct;90(2-3):203-9. doi: 10.1016/0021-9150(91)90116-k.
In the present study we investigated the influence of cholesterol depletion and hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibition on chemotaxis of the human monocytic cell line U937. Chemotaxis was nearly completely depressed after incubation for 24 h in the absence of lipoproteins. This was accompanied by a significant decrease in cellular cholesterol. Addition of 10 micrograms/ml low density lipoprotein (LDL) for 2 h to the cholesterol-depleted cells restored chemotaxis. Free cholesterol had no effect under these conditions. Inhibition of HMG-CoA reductase by pravastatin (0.01-1.0 mM) for 20 or 72 h also reduced chemotaxis. However, this effect was not accompanied by a decrease in cellular cholesterol when cells were grown in the presence of lipoproteins. The effect of pravastatin could be reversed by the addition of mevalonate. Addition of LDL did not change the response to pravastatin. We propose that the availability of cholesterol plays an important role in cellular chemotaxis. Furthermore, it can be suggested that other products of the mevalonate pathway apart from cholesterol may contribute to the regulation of chemotaxis.
在本研究中，我们调查了胆固醇耗竭和羟甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）抑制对人单核细胞系U937趋化性的影响。在无脂蛋白的情况下孵育24小时后，趋化性几乎完全受到抑制。这伴随着细胞胆固醇的显著降低。向胆固醇耗竭的细胞中添加10微克/毫升低密度脂蛋白（LDL）2小时可恢复趋化性。在这些条件下，游离胆固醇没有作用。普伐他汀（0.01 - 1.0毫摩尔）抑制HMG-CoA还原酶20或72小时也会降低趋化性。然而，当细胞在脂蛋白存在的情况下生长时，这种作用并不伴随着细胞胆固醇的降低。添加甲羟戊酸可逆转普伐他汀的作用。添加LDL不会改变对普伐他汀的反应。我们认为胆固醇的可利用性在细胞趋化性中起重要作用。此外，可以推测除胆固醇外，甲羟戊酸途径的其他产物可能有助于趋化性的调节。
