The Role Of Semaphorin 7A In Alternatively Activation Of Macrophages

Th2 cytokines contributes to the alternative activation of macrophages (M2 macrophages) which is closely related with asthma pathogenesis. Semaphorin 7A (Sema7A) plays a role in regulation of immune system as well as nervous system. However, the exact role of Sema7a on alveolar macrophages (AMs) in the pathogenesis of asthma is not fully understood. We examined the expression of Sema7A in macrophage of asthmatic airway and the effect of Sema7a in the Th2 cytokine stimulated alveolar macrophages in vitro. The expression of Sema7a was evaluated in induced sputum inflammatory cells from asthmatic patients compared with normal controls. The effect of Sema7a on alternative activation of macrophage was evaluated by comparing expression of M2 markers in the presence and absence of Sema7A siRNA. To see the direct effect of Sema7a on macrophage, IL-4 or IL-13-stimulated alveolar macrophages were treated with recombinant Sema7a. The mRNA expression of Sema7A was higher in induced sputum inflammatory cells from asthmatic patients than those from normal controls. However, sema 7a expression was lower in asthmatic patients with relatively severe airway hyperresponsiveness compared with asthmatic patients with mild airway hyperreponsiveness (P<0.05). Messenger RNA expression of key markers of alternatively activated macrophage (Ym-1, CD206, Arginase-1) was enhanced in treatment with Sema7A siRNA. On the other hand, recombinant Sema7a significantly suppressed IL-4/IL-13 induced the mRNA expression of Ym-1 and CD206. FACS analysis showed that IL-4/IL-13-induced arginase-1 expression was also inhibited by recombinant Sema7a. Sema7A may play some role in asthma inflammation by negatively regulating alternative activation of alveolar macrophages by IL-4 or IL-13 stimulation.