Abstract

Abstract It is well established that IL-4 induces alternative activation of macrophages involving intracellular activation of STAT6. Furthermore, it has been suggested that this cytokine has a proliferative effect on macrophages. On the other hand, there is evidence that pulmonary surfactant protein A (SP-A) plays an important role in modulating inflammatory response of alveolar macrophages (aMϕ). However, little is known about the effect of SP-A on the alternative activation of aMϕ. The aim of this study was to determine the effect of SP-A on aMϕ stimulated with IL-4. To accomplish this, purified rat aMϕ were stimulated with IL-4, different doses of SP-A, and combinations thereof. We measured arginase activity, cell viability, and STAT6 phosphorylation. We found that SP-A increased both IL-4-induced arginase activity and STAT6 phosphorylation. Finally, we observed more viable aMϕ in the presence of IL-4 and SP-A. We conclude that SP-A has a synergistic effect with IL-4 to lead aMϕ to an alternative activation. Furthermore, SP-A together with IL-4 may have either the protective effect of preventing aMϕ death or may cause cellular proliferation. Ongoing studies will allow us to discover the mechanism by which SP-A modulates the effect of IL-4 in aMϕ and determine if SP-A together with IL-4 causes either aMϕ survival or proliferation.

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