Mouse leukotriene A₄ hydrolase is expressed at high levels in intestinal crypt cells and splenic lymphocytes

LTA₄ hydrolase ( EC 3.3.2.6) is a dual-function enzyme that is essential for the conversion of leukotriene A₄ (LTA₄) to leukotriene B₄ (LTB₄ ) and also possesses an aminopeptidase activity. To characterize the expression of this unusual enzyme, we have cloned the mouse LTA₄ hydrolase cDNA. The deduced amino acid sequence revealed 92% identity with the human sequence. Cloning and analysis of genomic sequences of mouse LTA₄ hydrolase indicated that it is a single-copy gene spanning over 40 kb and containing 20 exons. LTA₄ hydrolase is widely expressed, with the highest levels of expression occurring in the small intestine, followed by the spleen. In situ hybridization revealed that LTA₄ hydrolase is localized in the crypt cells of the small intestine, white pulp of the spleen, bronchiolar epithelium of the lung, myocardium, adrenal cortex, epithelium of the seminal vesicles, proximal tubules and the collecting ducts of the kidney, and occasional hepatocytes. Thus the widespread distribution of LTA₄ hydrolase in various cell types in the tissues suggests that LTB₄ may possess biological activities other than those known at present. It is also plausible that the widespread occurrence of LTA₄ hydrolase in various tissues may correspond more with its function as an aminopeptidase than its function as an LTA 4 hydrolase. (C) 1999 Elsevier Science B.V. All rights reserved.