| First Author | Sender V | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 4 | Pages | 2397-411 |
| PubMed ID | 21248257 | Mgi Jnum | J:169141 |
| Mgi Id | MGI:4939942 | Doi | 10.4049/jimmunol.1002446 |
| Citation | Sender V, et al. (2011) Pulmonary surfactant protein A enhances endolysosomal trafficking in alveolar macrophages through regulation of Rab7. J Immunol 186(4):2397-411 |
| abstractText | 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 specifically 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(-/-) mice is significantly 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(-/-) mice. Activation of Rab7, but not Rab7b, by SP-A depends on the PI3K/Akt/protein kinase Czeta (PKCzeta) signal transduction pathway in AM and RAW264.7 macrophages. SP-A induces a Rab7/PKCzeta interaction in these cells, and the disruption of PKCzeta by small interfering RNA knockdown abolishes the effect of SP-A on Rab7. The data demonstrate a novel role for SP-A in modulating endolysosomal trafficking via Rab7 in primary AM and define biochemical pathways involved. |
