Alox15, 12/15-lipoxygenase, 12/15-LOX, or 12/15-LO). Both human ALOX15 and ALOX15B genes are located on chromosome 17; their product proteins have an amino acid sequence identity of only ~38%; they also differ in the polyunsaturated fatty acids that they prefer as substrates and exhibit different product profiles when acting on the same substrates. Tissue distribution Human ALOX15 protein is highly expressed in circulating blood eosinophils and reticulocytes, cells, bronchial airway epithelial cells, mammary epithelial cells, the Reed-Sternberg cells of Hodgkin's lymphoma, corneal epithelial cells, and dendritic cells; it is less strongly expressed in alveolar macrophages, tissue mast cells, tissue fibroblasts, circulating blood neutrophils, vascular endothelial cells, joint Synovial membrane cells, seminal fluid, prostate epithelium cells, and mammary ductal epithelial cells. The distribution of Alox15 in sub-human primates and, in particular, rodents differs significantly from that of human ALOX15; this, along with their different principal product formation (e.g. 12-HETE rather than 15-HETE) has made the findings of Alox15 functions in rat, mouse, or rabbit models difficult to extrapolate to the function of ALOX15 in humans. Enzyme activities Lipoxygenase activity ALOX15 and Alox15 enzymes are non-heme, iron-containing dioxygenases. They commonly catalyze the attachment of molecular oxygen as a peroxy residue to polyunsaturated fatty acids (PUFA) that contain two carbon-carbon double bonds that for the human ALOX15 are located between carbons 10 and 9 and 7 and 6 as numbered counting backward from the last or omega (i.e. ω) carbon at the methyl end of the PUFA (these carbons are also termed ω-10 and ω-9 and ω-7 and ω-6). In PUFAs that do not have a third carbon-carbon double bound between their ω-13 and ω-12 carbons, human ALOX15 forms ω-6 peroxy intermediates; in PUFAs that do have this third double bound, human ALOX15 makes the ω-6 peroxy intermediate but also small amounts of the ω-9 peroxy intermediate. Rodent Alox15 enzymes, in contrast, produce almost exclusively ω-9 peroxy intermediates. Concurrently, ALOX15 and rodent Alox15 enzymes rearrange the carbon-carbon double bonds to bring them into the 1S-hydroxy-2E,4Z-diene configuration. ALOX15 and Alox15 enzymes act with a high degree of Stereospecificity to form products that position the hydroperoxy residue in the S stereoisomer configuration. Lipohydroperoxidase activity Human ALOX15 can also convert the peroxy PUFA intermediate to a cyclic ether with a three-atom ring, i.e. an epoxide intermediate that is attacked by a water molecule to form epoxy-hydrpoxy PUFA products. Eoxins stimulate vascular permeability in an ex vivo human