SP-R210 (Myo18A) Isoforms as Intrinsic Modulators of Macrophage Priming and Activation

摘要: The surfactant protein (SP-A) receptor SP-R210 has been shown to increase phagocytosis of SP-A-bound pathogens and modulate cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity enhancing opsonization clearance modulating macrophage inflammatory responses. Alternative splicing the Myo18A gene results two isoforms: SP-R210S SP-R210L, with latter predominantly expressed alveolar macrophages. In this study we show that is required for optimal expression SP-R210L on Interestingly, pre-treatment prepared different methods either enhances or suppresses responsiveness LPS, possibly due differential co-isolation SP-B other proteins. We also report dominant negative disruption augments receptors including SR-A, CD14, CD36, macrophages’ response TLR stimulation. Finally, because known used a variety techniques investigate how mediates effect CD14. These studies revealed novel physical association between SP-R210S, SR-A leading enhanced found regulate internalization CD14 via distinct macropinocytosis-like mechanisms. Together, our findings support model which isoforms differentially trafficking, expression, activation innate