Journal of Clinical and Cellular Immunology
Open Access

Sex- and gene-specific differences in the acute in vivo effects of SP-A on the Mouse Alveolar Macrophage Proteome

International Conference on Innate Immunity

July 20-21, 2015 Barcelona, Spain

David S Phelps, Todd M Umstead, BS and Joanna Floros

Posters-Accepted Abstracts: J Clin Cell Immunol

Abstract :

Surfactant protein-A (SP-A) is involved in lung innate immunityand affects many alveolar macrophage (AM) functions. We previously demonstrated that SP-A knockout (KO) mice, particularly males, are more susceptible to pneumonia with Klebsiellapneumoniae. Humans have two closely related SP-A genes, SFTPA1 and SFTPA2, each with several variants. We examined the in vivo effects of treatment with specific SP-A variants on the AM proteome from SP-A KO mice. We hypothesized that the AM proteome is differentially affected by SP-A1 and SP-A2 in each sex. To test this hypothesis male and female KO mice received either SP-A1 or SP-A2, 18h later the AM were collected, and their proteomes examined by 2D-DIGE and mass spectrometry. We identified 90 proteins and categorized them as related to actin/cytoskeleton, oxidative stress, protease balance/chaperones, regulation of inflammation, and regulatory/developmental processes. SP-A1 and SP-A2 had different effects on the AM proteome and these effects differed between sexes. In males vs females more changes occurred in oxidative stress, protease/chaperones, and inflammation groups with SP-A2 treatment than with SP-A1. In females vs males more SP-A1-induced changes were in actin/cytoskeletal and oxidative stress groups. We conclude that after acute SP-A1 and SP-A2 treatment, sex-specific differences were observed in the AM proteomes from KO mice, and that these sex differences differ in response to SP-A1 and SP-A2. These effects may be responsible for sex differences in lung disease susceptibility. These observations demonstrate the therapeutic potential of exogenous SP-A and illustrate that sex- and gene-specific differences exist in the response to SP-A. Funding: Supportedin part by HL 34788 and ES009882 from the National Heart, Lung and Blood Institute and the National Institute of Environmental Health Sciences.