Linked Life Data

21248257

Source:http://linkedlifedata.com/resource/pubmed/id/21248257

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-3
pubmed: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 C? (PKC?) signal transduction pathway in AM and RAW264.7 macrophages. SP-A induces a Rab7/PKC? interaction in these cells, and the disruption of PKC? 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2397-411
pubmed:meshHeading
pubmed-meshheading:21248257-Animals, pubmed-meshheading:21248257-Cell Line, pubmed-meshheading:21248257-Cells, Cultured, pubmed-meshheading:21248257-Endosomes, pubmed-meshheading:21248257-Lysosomes, pubmed-meshheading:21248257-Macrophages, Alveolar, pubmed-meshheading:21248257-Male, pubmed-meshheading:21248257-Mice, pubmed-meshheading:21248257-Mice, Inbred C57BL, pubmed-meshheading:21248257-Mice, Knockout, pubmed-meshheading:21248257-Oncogene Protein v-akt, pubmed-meshheading:21248257-Phosphatidylinositol 3-Kinases, pubmed-meshheading:21248257-Protein Kinase C, pubmed-meshheading:21248257-Protein Transport, pubmed-meshheading:21248257-Proto-Oncogene Proteins c-akt, pubmed-meshheading:21248257-Pulmonary Surfactant-Associated Protein A, pubmed-meshheading:21248257-Rats, pubmed-meshheading:21248257-Rats, Sprague-Dawley, pubmed-meshheading:21248257-Signal Transduction, pubmed-meshheading:21248257-rab GTP-Binding Proteins
pubmed:year
2011
pubmed:articleTitle
Pulmonary surfactant protein A enhances endolysosomal trafficking in alveolar macrophages through regulation of Rab7.
pubmed:affiliation
Division of Cellular Pneumology, Department of Experimental Pneumology, Research Center Borstel, Leibniz Center for Medicine and Biosciences, 23845 Borstel, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't