Marked differences in tissue-specific expression of chitinases in mouse and man.
Two distinct chitinases have been identified in mammals: a phagocyte-specific enzyme named chitotriosidase and an acidic mammalian chitinase (AMCase) expressed in the lungs and gastrointestinal tract. Increased expression of both chitinases has been observed in different pathological conditions: chitotriosidase in lysosomal lipid storage disorders like Gaucher disease and AMCase in asthmatic lung disease. Recently, it was reported that AMCase activity is involved in the pathogenesis of asthma in an induced mouse model. Inhibition of chitinase activity was found to alleviate the inflammation-driven pathology. We studied the tissue-specific expression of both chitinases in mice and compared it to the situation in man. In both species AMCase is expressed in alveolar macrophages and in the gastrointestinal tract. In mice, chitotriosidase is expressed only in the gastrointestinal tract, the tongue, fore-stomach, and Paneth cells in the small intestine, whereas in man the enzyme is expressed exclusively by professional phagocytes. This species difference seems to be mediated by distinct promoter usage. In conclusion, the pattern of expression of chitinases in the lung differs between mouse and man. The implications for the development of anti-asthma drugs with chitinases as targets are discussed.
Boot
Rolf G
RG
Department of Biochemistry, University of Amsterdam Academic Medical Center, The Netherlands. r.g.boot@amc.uva.nl
Bussink
Anton P
AP
Verhoek
Marri
M
de Boer
Piet A J
PA
Moorman
Antoon F M
AF
Aerts
Johannes M F G
JM
D000818:Animals; D019556:COS Cells; D002688:Chitinases / Q000096:biosynthesis* / Q000235:genetics; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D006596:Hexosaminidases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D012333:RNA, Messenger; D006596:Hexosaminidases; C086400:chitotriosidase; C499255:AMCase, mouse; C499254:CHIA protein, human; D002688:Chitinases