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SEMA4A Contributes Eosinopillic Phenotypes in Asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Yohei Maeda, Masaki Hayama, Kazuya Takeda, Atsushi Kumanogoh, Hidenori Inohara
Rationale:

We previously reported that the class IV semaphorin SEMA4A was critical for Th1/Th2 regulation and that eosinophilic airway inflammation was enhanced in SEMA4A-deficient mice. However, the role of SEMA4A in eosinophils and human eosinophilic airway inflammation is still unknown.

Methods:

We compared serum SEMA4A levels in patients with asthma and CRSwNP vs healthy individuals by enzyme-linked immunosorbent assay (ELISA), and examined SEMA4A expression in nasal polyps by immunohistochemistry. We cultured bone marrow cells from Wild Type mice (WT mice) and SEMA4A-deficient mice with recombinant IL-5, and evaluated the recovery of the bone marrow-derived eosinophils (BMDEos). In addition, we determined the number of eosinophils in the spleen from WT mice or SEMA4A-deficient mice.

Results:

Levels of SEMA4A were significantly elevated in sera from patients with asthma and CRSwNP than healthy individuals. (mean±SEM 3588±840 and 2403±618 versus 445±214). We found that SEMA4A was strongly expressed in eosinophils in the nasal polyps by immunohistochemistry. BMDEos and the number of splenic eosinophils from SEMA4A-deficient mice were significantly lower than those from WT mice (mean±SEM 2.14±0.23×107 versus 1.41±0.10×107, 5973±189/106 versus 4100±750/106, respectively).

Conclusions:

Our results suggested that SEMA4A had trophic functions for eosinophils in human and mice. SEMA4A may promote eosinophil survival and disease activity in patients with asthma and CRSwNP.