Sensory system-predominant distribution of leukotriene A4 hydrolase and its colocalization with calretinin in the mouse nervous system

Leukotriene 134 is a potent lipid mediator, which has been identified as a potent proinflammatory and immunomodulatory compound. Although there has been robust evidence indicating that leukotriene 134 is synthesized in the normal brain, detailed distribution and its functions in the nervous system have been unclear. To obtain insight into the possible neural function of leukotriene 1341 we examined the immunohistochemical distribution of leukotriene A(4) hydrolase, an enzyme catalyzing the final and committed step in leukotriene B-4 biosynthesis, in the mouse nervous system. Immunoreactivity for leukotriene A4 hydrolase showed widespread distribution with preference to the sensory-associated structures; i.e. neurons in the olfactory epithelium and vomeronasal organ, olfactory glomeruli, possibly amacrine cells, neurons in the ganglion cell layer and three bands in the inner plexiform layer of the retina, axons in the optic nerve and tract up to the superior colliculus, inner and outer hair cells and the spiral ganglion cells in the cochlea, vestibulocochlear nerve bundle, spinal trigeminal tract, and lamina 11 of the spinal cord. Double immunofluorescence staining demonstrated that most of the leukotriene A(4)-hydrolase-immunopositive neurons coexpressed calretinin, a calcium-binding protein in neurons. The ubiquitous distribution of leukotriene A4 hydrolase was in sharp contrast with the distribution of leukotriene C-4 synthase [Shimada A, Satoh M, Chiba Y, Saitoh Y, Kawamura N, Keino H, Hosokawa M, Shimizu T (2005) Highly selective localization of leukotriene C4 synthase in hypothalamic and extrahypothalamic vasopressin systems of mouse brain. Neuroscience 131:683-689] which was confined to the hypothalamic and extrahypothalamic vasopressinergic neurons. These results suggest that leukotriene 134 may exert some neuromodulatory function mainly in the sensory nervous system, in concert with calretinin. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.