Role of acidic mammalian chitinase and chitotriosidase in nasal polyps

Department of Otorhinolaryngology-Head and Neck Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
Otolaryngology Head and Neck Surgery (Impact Factor: 2.02). 10/2009; 141(4):462-6. DOI: 10.1016/j.otohns.2009.06.013
Source: PubMed


Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and helminth immunity, and this process can be negatively regulated by vertebrate chitinases. Acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) have chitinolytic activity, but little is known about their roles in nasal polyps.
A prospective controlled study.
A tertiary referral center.
Nineteen subjects with nasal polyps and 12 subjects with deviated nasal septums were recruited to obtain inferior turbinate mucosa samples. The expression levels of AMCase and ChT were compared in nasal polyp and inferior turbinate tissue samples. The tissue samples were analyzed by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical staining.
AMCase and ChT were detected in all nasal polyps and inferior turbinate tissues. AMCase and ChT messenger RNA and protein expression were significantly higher in nasal polyps than in inferior turbinate tissues. In nasal polyps, AMCase-positive and ChT-positive cells were detected in the epithelium, inflammatory cells, and submucosal gland.
AMCase and ChT may be important mediators in the pathogenesis of nasal polyps. Nasal polyps appear to have elevated levels of chitinases, and the presence or growth of chitin-containing pathogens might enhance chitinase expression, resulting in nasal polyp formation and growth in susceptible individuals.

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    ABSTRACT: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and immunity. This process can be negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) have chitinolytic activity. This study aimed to determine the activities of AMCase and ChT in nasal polyps (NPs), as well as their in situ localization in NP tissue. AMCase and ChT activities in NPs were compared with those in inferior turbinate tissue samples. Tissue samples were measured for AMCase and ChT activities at a range of pHs using the fluorogenic substrate 4-methylumbelliferyl-beta-d-N,N',N''-triacetyl-chitotriose. Double immunofluorescent staining for the localization of both AMCase and ChT was performed using NP cryosections. Both AMCase and ChT displayed markedly increased chitinolytic activity in all NPs, compared with inferior turbinate tissues. Double immunofluorescent staining revealed that CD68 highlighted monocytes in the submucosa of NP and these cells disclosed coexpression of AMCase and ChT. CD31 detected capillary endothelial cells, but did not express any AMCase and ChT. The increased chitinolytic activities of AMCase and ChT in NPs may be important in NP pathogenesis, suggesting that inhibition of chitinolytic activity may be a novel therapeutic strategy for the treatment of NPs.
    American Journal of Rhinology and Allergy 01/2011; 25(1):12-4. DOI:10.2500/ajra.2011.25.3555 · 1.81 Impact Factor
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    ABSTRACT: Chronic rhinosinusitis with nasal polyps (CRSwNP) is connected to a chronic inflammatory process with the activation of different immune components. Eotaxin-3, acidic mammalian chitinase (AMCase), and interleukin (IL)–13 as focal immune factors have been detected in CRSwNP, but their importance and relationship are still being investigated. This study aims to detect the expression of AMCase, IL-13, and eotaxin-3 in the mRNA level and investigate their roles and relationships in CRSwNP. Twenty-four subjects with eosinophilic CRSwNP and 11 controls were included in the study. Tissues were obtained by endoscopic sinus surgery. Target genes were detected by real-time reverse transcription–polymerase chain reaction. AMCase, eotaxin-3, and IL-13 were detected in all CRSwNP and controls. The expression of AMCase, eotaxin-3, IL-13, and mRNA was significantly higher in patients with CRSwNP than in the control group. There was a significantly positive correlation not only between AMCase and eotaxin-3 but also between IL-13 and eotaxin-3 in CRSwNP. Increased AMCase, IL-13, and eotaxin-3 might lead to the Th2 inflammatory cascade reaction.
    Otolaryngology Head and Neck Surgery 03/2011; 145(2):324-6. DOI:10.1177/0194599811403077 · 2.02 Impact Factor
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    ABSTRACT: An important role for B cells and immunoglobulin deposition in the inflammatory tumor cell environment has been recognized in several cancers, and this is recapitulated in our murine model of inflammation-associated carcinogenesis: transgenic mice expressing the Epstein-Barr virus oncogene LMP1 in epithelia. Similarly in several autoimmune disorders, immunoglobulin deposition represents a key underlying event in the disease process. However, the autoantigens in most cases are not known. In other studies, overexpression of the enzymatically inactive mammalian chitinase-like proteins (CLPs) has been observed in a number of autoimmune disorders and numerous cancers, with expression correlated with poor prognosis, although the function of these proteins is largely unknown. We have now linked these observations demonstrating that overexpression of the CLPs renders them the targets for autoantigenicity during carcinogenic progression. We show that the CLPs, Chi3L1, Chi3L3 /YM1, and Chi3L4/YM2, are abundantly overexpressed in the transgenic epidermis at an early, preneoplastic stage and secreted into the serum. Immunoglobulin G reactive to the CLPs is detected in the serum and deposited in the hyperplastic tissue, which goes on to become inflamed and progressively displastic. The CLPs are also upregulated in chemical carcinogen-promoted lesions in both transgenic and wild-type mice. Expression of the related, active chitinases, Chit1 and AMCase, increases following infiltration of inflammatory cells. In this model, the 3 CLPs are autoantigens for the tissue-deposited immunoglobulin, which we propose plays a causative role in promoting the inflammation-associated carcinogenesis. This may reflect their normal, benign function to promote tissue remodeling and to amplify immune responses. Their induction during carcinogenesis and consequent autoantigenicity provides a missing link between the oncogenic event and subsequent inflammation. This study identifies the CLPs as important and novel therapeutic targets to limit inflammation in cancer and potentially also autoimmune disorders.
    Genes & cancer 05/2011; 2(1):74-87. DOI:10.1177/1947601911402681
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