Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

Nadel, Jay A.; Conrad, Douglas; Ueki, Iris F.; Schuster, Anne; Sigal, Elliott

doi:10.1172/jci115110

Cited by 107 publications

(53 citation statements)

References 25 publications

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“…In human skin, we have now established the occurrence of both types of 15S-lipoxygenase. In lung, the 15-HETE synthesis has been ascribed to the blood cell type of 15-lipoxygenase (35) and this enzyme has been detected by immunohistochemistry (36)(37)(38), but clearly the possibility that the new 15-lipoxygenase contributes to the synthesis in certain cell types should be reexamined. Our finding of the mRNA in prostate is compatible with the reports by Oliw and colleagues of the occurrence of 15-lipoxygenase in prostasomes, components of semen secreted by the prostate gland (39,40).…”

Section: Discussionmentioning

confidence: 99%

Discovery of a second 15 S -lipoxygenase in humans

Brash

Boeglin

Chang

1997

Proc. Natl. Acad. Sci. U.S.A.

375

337

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The lipoxygenase metabolism of arachidonic acid occurs in specific blood cell types and epithelial tissues and is activated in inf lammation and tissue injury. In the course of studying lipoxygenase expression in human skin, we detected and characterized a previously unrecognized enzyme that at least partly accounts for the 15S-lipoxygenase metabolism of arachidonic acid in certain epithelial tissues. The cDNA was cloned from human hair roots, and expression of the mRNA was detected also in prostate, lung, and cornea; an additional 16 human tissues, including peripheral blood leukocytes, were negative for the mRNA. The cDNA encodes a protein of 676 amino acids with a calculated molecular mass of 76 kDa. The amino acid sequence has approximately 40% identity to the known human 5S-, 12S-, and 15S-lipoxygenases. When expressed in HEK 293 cells, the newly discovered enzyme converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while linoleic acid is less well metabolized. These features contrast with the previously reported 15S-lipoxygenase, which oxygenates arachidonic acid mainly at C-15, but also partly at C-12, and for which linoleic acid is an excellent substrate. The different catalytic activities and tissue distribution suggest a distinct function for the new enzyme compared with the previously reported human 15S-lipoxygenase.

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Section: Discussionmentioning

confidence: 99%

Discovery of a second 15 S -lipoxygenase in humans

Brash

Boeglin

Chang

1997

Proc. Natl. Acad. Sci. U.S.A.

375

337

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“…Antibodies included rabbit anti-5 LO (LO-32, a gift of Dr. Jilly Evans, Merck Frosst, Pointe Claire-Dorval, Quebec) and rabbit anti-15-LO (a gift of Dr. Elliot Sigal) [16]. The specificities of the antibodies for 5-LO [9,17,18] and 15-LO [16,19], respectively, have been previously characterized. The anti-phosphotyrosine antibodies, PY-20 and 4G10, were from Transduction Laboratories (Lexington, KY) and Upstate Biotechnology, Inc. (Lake Placid, NY), respectively.…”

Section: Methodsmentioning

confidence: 99%

Pathways for eosinophil lipid body induction: differing signal transduction in cells from normal and hypereosinophilic subjects

Bozza

Cassara

et al. 1998

Journal of Leukocyte Biology

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“…2 and 3). 12/15-LO is generally considered to be a cytosolic enzyme (30). It lacks obvious membrane binding domains.…”

Section: /15-lipoxygenase Targets Actin Polymerizationmentioning

confidence: 99%

12/15-Lipoxygenase Translocation Enhances Site-specific Actin Polymerization in Macrophages Phagocytosing Apoptotic Cells

Miller¹,

Chang²,

Funk

et al. 2001

Journal of Biological Chemistry

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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-Lipoxygenase (LO)1 is a member of the LO family of enzymes that insert peroxyl groups into double bonds of free and phospholipid-bound polyunsaturated fatty acids. The exact role of these enzymes in biological processes has remained elusive, but increasingly evidence has accumulated that they play important roles in specific cellular functions. For example, 15-LO activity in reticulocytes at the stage of organelle degradation may contribute to membrane destabilization and contribute to pore formation in intracellular membranes (1, 2). Fatty acid products of 12/15-LO are powerful agonists for the nuclear receptor PPAR-␥, which helps regulate glucose metabolism and adipocyte and macrophage differentiation and function (3). A remarkable feature of 12/15-LO is that its expression is not constant during the cell life span but rather turns on at certain points during cell development. While circulating human monocytes do not express 15-LO, monocyte-derived macrophages exposed to interleukin-4 or interleukin-13 express 15-LO (4, 5). In addition, mouse macrophages residing for a long time in the peritoneum (resident macrophages) also highly express the mouse homologue, 12/15-LO, although the pathway leading to 12/15-LO expression may differ somewhat from that which occurs with human monocytes (6).Macrophages of atherosclerotic lesions express high levels of 15-LO (7), and recent evidence utilizing apoE Ϫ/Ϫ mice in which the 12/15-LO gene was disrupted demonstrated its importance in the pathogenesis of atherosclerosis (8). Another characteristic of atherosclerotic tissue but not of normal vascular wall is the high abundance of apoptotic cells (9). This fact might reflect either an increased rate of formation of such cells, a decreased rate of clearance, for example by arterial macrophages, or both. In either case, phagocytosis and the degradation and metabolism of th...

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Immunocytochemical localization of arachidonate 15-lipoxygenase in erythrocytes, leukocytes, and airway cells.

Cited by 107 publications

References 25 publications

Discovery of a second 15 S -lipoxygenase in humans

Discovery of a second 15 S -lipoxygenase in humans

Pathways for eosinophil lipid body induction: differing signal transduction in cells from normal and hypereosinophilic subjects

12/15-Lipoxygenase Translocation Enhances Site-specific Actin Polymerization in Macrophages Phagocytosing Apoptotic Cells

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