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An inhibitor of leukotriene-A₄ hydrolase from bat salivary glands facilitates virus infection.

ABSTRACT: SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A₄ hydrolase (LTA₄H) to produce the lipid chemoattractant leukotriene B₄ (LTB₄), was identified and characterized from the submandibular salivary glands of the bat Myotis pilosus. To the best of our knowledge, this is a report of an endogenous LTA₄H inhibitor in animals. MTX was highly concentrated in the bat salivary glands, suggesting a mechanism for the generation of immunological privilege and immune tolerance and providing evidence of viral shedding through oral secretions. Moreover, given that the immunosuppressant MTX selectively inhibited the proinflammatory activity of LTA₄H, without affecting its antiinflammatory activity, MTX might be a potential candidate for the development of antiinflammatory drugs by targeting the LTA₄-LTA₄H-LTB₄ inflammatory axis.

SUBMITTER: Fang M

PROVIDER: S-EPMC8915838 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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An inhibitor of leukotriene-A4 hydrolase from bat salivary glands facilitates virus infection.

Fang Mingqian M Tang Xiaopeng X Zhang Juan J Liao Zhiyi Z Wang Gan G Cheng Ruomei R Zhang Zhiye Z Zhao Hongwen H Wang Jing J Tan Zhaoxia Z Kamau Peter Muiruri PM Lu Qiumin Q Liu Qi Q Deng Guohong G Lai Ren R

Proceedings of the National Academy of Sciences of the United States of America 20220301 10

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A4 hydrolase (LTA4H) to produce the lipid chemoattractant leukotriene B4 (LTB4), was identified and characterized from the submandibular salivary glands of the bat Myotis pilosus. To the best of our knowledge, this is a report of an endogenous LTA4H inhibitor in animals. MTX was highly concentrated in the bat salivary glands, su ...[more]

PMID: 35238649

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Project description:BackgroundAllergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs.MethodsArtemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders.ResultsArtemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT.ConclusionSerum LTA4H may be a potential biomarker for early prediction of an effective AIT.

Dataset Information

An inhibitor of leukotriene-A₄ hydrolase from bat salivary glands facilitates virus infection.

Publications

An inhibitor of leukotriene-A<sub>4</sub> hydrolase from bat salivary glands facilitates virus infection.

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