Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit.
BACKGROUND
Chitinolytic enzymes play important roles in the pathophysiology of allergic airway responses in mouse models of asthma. Acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT1) have chitinolytic activity, but relatively little is known about their expression in human asthma.


OBJECTIVE
We sought to determine the expression and activity of AMCase and CHIT1 in healthy subjects, subjects with asthma, and habitual smokers, taking account of the null 24-bp duplication in the CHIT1 gene.


METHODS
We measured chitinase activity in bronchoalveolar lavage (BAL) fluid at multiple pHs by using a synthetic chitin substrate. We also determined AMCase and CHIT1 gene expression in epithelial brushings and BAL fluid macrophages by means of real time RT-PCR. Paired DNA samples were genotyped for the CHIT1 duplication.


RESULTS
In all subgroups the pH profile of chitinase activity in BAL fluid matched that of CHIT1, but not AMCase, and chitinase activity was absent in subjects genetically deficient in active CHIT1. Although AMCase protein was detectable in lavage fluid, AMCase transcripts in macrophages were consistent with an isoform lacking enzymatic activity. Median chitinase activity in BAL fluid tended to be lower than normal in asthmatic subjects but was increased 7-fold in habitual smokers, where CHIT1 gene expression in macrophages was increased.


CONCLUSIONS
Chitinase activity in the lung is the result of CHIT1 activity. Although AMCase protein is detectable in the lung, our data indicate that it is inactive. Chitinase activity is not increased in subjects with asthma and in fact tends to be decreased. The high levels of chitinase activity in habitual smokers result from upregulation of CHIT1 gene expression, especially in macrophages.
Seibold
Max A
MA
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA 94143, USA.
Donnelly
Samantha
S
Solon
Margaret
M
Innes
Anh
A
Woodruff
Prescott G
PG
Boot
Rolf G
RG
Burchard
Esteban González
EG
Fahy
John V
JV
D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002688:Chitinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005838:Genotype; D006596:Hexosaminidases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000378:metabolism; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D006596:Hexosaminidases; C086400:chitotriosidase; C499254:CHIA protein, human; D002688:Chitinases