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Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.

ABSTRACT: We have previously shown that group V secretory phospholipase A(2) (sPLA(2)) regulates phagocytosis of zymosan and Candida albicans by a mechanism that depends on fusion of phagosomes with late endosomes in macrophages. In this study, we report that group V sPLA(2) (Pla2g5)-null mice exposed to an extract of house dust mite Dermatophagoides farinae had markedly reduced pulmonary inflammation and goblet cell metaplasia compared with wild-type (WT) mice. Pla2g5-null mice had also impaired Th2-type adaptive immune responses to D. farinae compared with WT mice. Pla2g5-null bone marrow-derived dendritic cells (BMDCs) activated by D. farinae had delayed intracellular processing of allergen and impaired allergen-dependent maturation, a pattern recapitulated by the native lung DCs of D. farinae-challenged mice. Adoptively transferred D. farinae-loaded Pla2g5-null BMDCs were less able than D. farinae-loaded WT BMDCs to induce pulmonary inflammation and Th2 polarization in WT mice. However, Pla2g5-null recipients transferred with WT or Pla2g5-null D. farinae-loaded BMDCs exhibited significantly reduced local inflammatory responses to D. farinae, even though the transfer of WT BMDCs still induced an intact Th2 cytokine response in regional lymph nodes. Thus, the expression of group V sPLA(2) in APCs regulates Ag processing and maturation of DCs and contributes to pulmonary inflammation and immune response against D. farinae. Furthermore, an additional yet to be identified resident cell type is essential for the development of pulmonary inflammation, likely a cell in which group V sPLA(2) is upregulated by D. farinae, and whose function is also regulated by group V sPLA(2).

SUBMITTER: Giannattasio G

PROVIDER: S-EPMC3003260 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.

Giannattasio Giorgio G Fujioka Daisuke D Xing Wei W Katz Howard R HR Boyce Joshua A JA Balestrieri Barbara B

Journal of immunology (Baltimore, Md. : 1950) 20100903 7

We have previously shown that group V secretory phospholipase A(2) (sPLA(2)) regulates phagocytosis of zymosan and Candida albicans by a mechanism that depends on fusion of phagosomes with late endosomes in macrophages. In this study, we report that group V sPLA(2) (Pla2g5)-null mice exposed to an extract of house dust mite Dermatophagoides farinae had markedly reduced pulmonary inflammation and goblet cell metaplasia compared with wild-type (WT) mice. Pla2g5-null mice had also impaired Th2-type ...[more]

PMID: 20817863

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Project description:BackgroundOne of the important pathogeneses of eustachian tube dysfunction (ETD) is nasal inflammatory disease. The prevalence of allergic rhinitis (AR) in adults ranges from 10 to 30% worldwide. However, research on the status of eustachian tubes in AR patients is still very limited.MethodsThis prospective controlled cross-sectional study recruited 59 volunteers and 59 patients with AR from Sun Yat-sen Memorial Hospital. Visual analogue scale (VAS) scores for AR symptoms and seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores were collected for both groups. Nasal endoscopy, tympanography and eustachian tube pressure measurement (tubomanometry, TMM) were used for objective assessment. All AR patients underwent 1 month of treatment with mometasone furoate nasal spray and oral loratadine. Then, the nasal condition and eustachian tube status were again evaluated.ResultsTMM examination revealed that 22 patients (39 ears, 33.1%) among the AR patients and 5 healthy controls (7 ears, 5.9%) had abnormal eustachian pressure. Twenty-two AR patients (37.3%) and 9 healthy controls had an ETDQ-7 score ≥ 15. With regard to nasal symptoms of AR, the VAS scores of nasal obstruction were correlated with the ETDQ-7 scores, and the correlation coefficient was r = 0.5124 (p < 0.0001). Nasal endoscopic scores were also positively correlated with ETDQ-7 scores, with a correlation coefficient of 0.7328 (p < 0.0001). After 1 month of treatment, VAS scores of nasal symptoms, endoscopic scores and ETDQ-7 scores were significantly decreased in AR patients (p < 0.0001), and TMM examination also suggested that eustachian tube function was significantly improved after treatment (p < 0.0001).ConclusionsAR patients, especially those with severe nasal obstruction, could have ETD. The local conditions of the pharyngeal orifices of the eustachian tubes are closely related to the symptoms of ETD. After treatment with nasal glucocorticoids and oral antihistamines, eustachian tube function can significantly improve as nasal symptoms subside.Trial registration Chinese Clinical Trial Registery (ChiCTR2000029071) Registered 12 January 2020-Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=48328&htm=4.

Dataset Information

Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.

Publications

Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.

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