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Sclerosing mesenteritis is a rare inflammatory and fibrosing disorder of unknown etiology, while IgG4-related disease (IgG4-RD) consists of mass-forming, fibroinflammatory lesions characterized by high serum IgG4 levels and tissue infiltration of many IgG4-positive plasma cells; obliterative phlebitis is common. This report describes a case of sclerosing mesenteritis that was considered a manifestation of IgG4-RD. A 53-year-old man underwent right hemicolectomy because of an ileocecal mass that did not improve with conservative therapy. The ill-defined fibroinflammatory lesion extended in the mesentery with storiform fibrosis, obliterative phlebitis, and infiltration of many IgG4-positive plasma cells. The ratio of IgG4-positive/IgG-positive cells was 64%, and the ratio of forkhead box protein 3 (FOXP3)-positive/CD4-positive cells was elevated (13%). It is likely that at least some cases of sclerosing mesenteritis are a manifestation of IgG4-RD. It is important to investigate this relationship because steroid therapy may benefit such cases.

To establish a role of the 12-lipoxygenase on the generation of oxidized low density lipoprotein (LDL) in macrophages that leads to foam cell formation in atherosclerosis, we overexpressed 12-lipoxygenases in a macrophage-like cell line, J774A.1, that does not show intrinsic enzyme activity. When the 12-lipoxygenaseexpressing cells were incubated with 400 mg´mL 21 LDL in Dulbecco's modified Eagle's medium at 37 8C for 12 h, LDL oxidation, as determined by thiobarbituric acid reactive substance, was markedly increased compared with the mock-transfected cells. Oxygenated products in the modified LDL were examined by HPLC before and after alkaline hydrolysis. Most of the oxygenated derivatives were of an esterified form, and the major product was identified as 13S-hydroxyoctadeca-9Z,11E-dienoic acid. These results clearly demonstrate that esterified fatty acids in LDL are oxygenated by the 12-lipoxygenases expressed in the J774A.1 cells. Furthermore, the oxidized LDL generated by intracellular 12-lipoxygenases was recognized by a scavenger receptor as assessed by macrophage degradation assay.

The oxidative modification of low density lipoprotein (LDL) has been implicated in the early stage of atherosclerosis through multiple potential pathways, and 12/ 15-lipoxygenase is suggested to be involved in this oxidation process. We demonstrated previously that the 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was required for the cell-mediated LDL oxidation. However, the mechanism of the oxidation of extracellular LDL by the intracellular 12/ 15-lipoxygenase has not yet been elucidated. In the present study, we found that not only the LDL receptor but also LDL receptor-related protein ( Lipoxygenases are a class of enzymes that incorporate one molecular oxygen into unsaturated fatty acids giving rise to their hydroperoxy derivatives. There are 5-, 8-, 12-, and 15-lipoxygenases in mammalian tissues, named according to the number of carbon atoms of arachidonic acid to be oxygenated (1-4). The 12-lipoxygenase subfamily includes leukocyte, platelet, and epidermal isoforms. 15-Lipoxygenase-1 was first isolated from reticulocytes, and 15-lipoxygenase-2 was cloned from hair follicles (3). Because the leukocyte 12-lipoxygenase and 15-lipoxygenase-1 are highly related in their primary structures and enzymological properties and are abundant in various tissues of many species, these enzymes are called collectively 12/15-lipoxygenases (2, 5). Although the pathophysiological functions of the 12/15-lipoxygenases are still a subject of investigation and discussion, recent research progress has revealed the involvement of the enzymes in the development of atherosclerosis (6 -8).The oxidative modification of low density lipoprotein (LDL) We previously demonstrated that 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was involved essentially in the oxidation of LDL based upon the stereospecific oxygenation of esterified unsaturated fatty acid in LDL (21). This fact suggests direct interaction of the enzyme with LDL or the transfer of cellular lipids oxygenated by the enzyme to LDL. Secretion or leakage of the 12/15-lipoxygenase to the medium was ruled out (21). As the mechanism of the cell-mediated oxidation of extracellular LDL, we postulate that binding of native LDL to cell surface receptors is the first step in the 12/15-lipoxygenase-expressing cells. Among such receptors, the LDL receptor plays an important role in LDL metabolism in liver and steroidogenic tissues. However, the LDL receptor is not expressed in the intima of normal or atherosclerotic arteries (22). Importantly, the LDL receptor is not required in the cell-mediated LDL oxidation as shown by in vitro experiments (23) and LDL receptor-deficient mice studies (20,24). The native LDL also binds to LDL receptor-related protein

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