Miller Y I, Chang M K, Funk C D, Feramisco J R, Witztum J L
Division of Endocrinology and Metabolism, Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
J Biol Chem. 2001 Jun 1;276(22):19431-9. doi: 10.1074/jbc.M011276200. Epub 2001 Mar 6.
The enzyme 12/15-lipoxygenase (12/15-LO) introduces peroxyl groups in a position-specific manner into unsaturated fatty acids in certain cells, but the role of such enzymatic lipid peroxidation remains poorly defined. Here we report a novel function for 12/15-LO in mouse peritoneal macrophages. When macrophages were coincubated with apoptotic cells, the enzyme translocated from cytosol to the plasma membrane and was more extensively concentrated at sites where macrophages bound apoptotic cells, colocalizing with polymerized actin of emerging filopodia. Disruption of F-actin did not prevent the 12/15-LO translocation. In contrast, inhibition of the 12/15-LO activity, or utilization of genetically engineered macrophages in which the 12/15-LO gene has been disrupted, greatly reduced actin polymerization in phagocytosing macrophages. Lysates of 12/15-LO-deficient macrophages had significantly lower ability to promote in vitro actin polymerization than the lysates of wild type macrophages. These studies suggest that the 12/15-LO enzyme plays a major role in local control of actin polymerization in macrophages in response to interaction with apoptotic cells.
12/15-脂氧合酶（12/15-LO）可将过氧基以位置特异性方式引入某些细胞中的不饱和脂肪酸，但这种酶促脂质过氧化作用的角色仍未明确界定。在此，我们报告12/15-LO在小鼠腹腔巨噬细胞中的一种新功能。当巨噬细胞与凋亡细胞共同孵育时，该酶从胞质溶胶转位至质膜，并更广泛地集中于巨噬细胞与凋亡细胞结合的部位，与新生丝状伪足的聚合肌动蛋白共定位。F-肌动蛋白的破坏并未阻止12/15-LO的转位。相反，抑制12/15-LO活性，或利用12/15-LO基因已被破坏的基因工程巨噬细胞，会大大降低吞噬巨噬细胞中的肌动蛋白聚合。12/15-LO缺陷巨噬细胞的裂解物促进体外肌动蛋白聚合的能力明显低于野生型巨噬细胞的裂解物。这些研究表明，12/15-LO酶在巨噬细胞中响应与凋亡细胞的相互作用而对肌动蛋白聚合进行局部控制中起主要作用。
