摘要：

Surfactant protein A (SP-A), the most abundant pulmonary soluble collectin, modulates innate and adaptive immunity of the lung, partially via its direct effects on alveolar macrophages (AM), the most predominant intra-alveolar cells under physiological conditions. Enhanced phagocytosis and endocytosis are key functional consequences of AM/SP-A interaction, suggesting a SP-A– mediated modulation of small Rab (Ras related in brain) GTPases that are pivotal membrane organizers in both processes. In this article, we show that SP-A specically and transiently enhances the protein expression of endogenous Rab7 and Rab7b, but not Rab5 and Rab11, in primary AM from rats and mice. SP-A–enhanced GTPases are functionally active as determined by increased interaction of Rab7 with its downstream effector Rab7 interacting lysosomal protein (RILP) and enhanced maturation of cathepsin-D, a function of Rab7b. In AM and RAW264.7 macrophages, the SP-A–enhanced lysosomal delivery of GFP- Escherichia coli is abolished by the inhibition of Rab7 and Rab7 small interfering RNA transfection, respectively. The constitutive expression of Rab7 in AM from SP-A 2 / 2 mice is signicantly reduced compared with SP-A +/+ mice and is restored by SP-A. Rab7 blocking peptides antagonize SP-A–rescued lysosomal delivery of GFP- E. coli in AM from SP-A 2 / 2 mice. Activation of Rab7, but not Rab7b, by SP-A depends on the PI3K/Akt/protein kinase C z (PKC z ) signal transduction pathway in AM and RAW264.7 macrophages. SP-A induces a Rab7/PKC z interaction in these cells, and the disruption of PKC interfering RNA knockdown abolishes the effect of SP-A on Rab7. The data demonstrate a novel role for SP-A in modulating endolysosomal trafcking via Rab7 in primary AM and dene biochemical pathways involved.

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