title: Differences in the alveolar macrophage proteome in transgenic mice expressing human SP-A1 and SP-A2.
abstract: Surfactant protein A (SP-A) plays a number of roles in lung host defense and innate immunity. There are two human genes,SFTPA1andSFTPA2, and evidence indicates that the function of SP-A1 and SP-A2 proteins differ in several respects. To investigate the impact of SP-A1 and SP-A2 on the alveolar macrophage (AM) phenotype, we generated humanized transgenic (hTG) mice on the SP-A knockout (KO) background, each expressing human SP-A1 or SP-A2. Using two-dimensional difference gel electrophoresis (2D-DIGE) we studied the AM cellular proteome. We compared mouse lines expressing high levels of SPA1, high levels of SP-A2, low levels of SP-A1, and low levels of SP-A2, with wild type (WT) and SP-A KO mice. AM from mice expressing high levels of SP-A2 were the most similar to WT mice, particularly for proteins related to actin and the cytoskeleton, as well as proteins regulated by Nrf2. The expression patterns from mouse lines expressing higher levels of the transgenes were almost the inverse of one another - the most highly expressed proteins in SP-A2 exhibited the lowest levels in the SP-A1 mice and vice versa. The mouse lines where each expressed low levels of SP-A1 or SP-A2 transgene had very similar protein expression patterns suggesting that responses to low levels of SP-A are independent of SP-A genotype, whereas the responses to higher amounts of SP-A are genotype-dependent. Together these observations indicate that in vivo exposure to SP-A1 or SP-A2 differentially affects the proteomic expression of AMs, with SP-A2 being more similar to WT.
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Phelps
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Silveyra
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Sanmei
authors.initials: S
authors.lastname: Hu
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
authors.affiliation: C enter for H ost defense, I nflammation, and L ung D isease (CHILD) Research and Departments of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. ; Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
keywords: 2D-DIGE; collectin; host defense; lung; surfactant
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