title: Sex differences in the acute in vivo effects of different human SP-A variants on the mouse alveolar macrophage proteome.
abstract: Surfactant protein A (SP-A) is involved in lung innate immunity. Humans have two 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 alveolar macrophage (AM) proteome from SP-A knockout (KO) mice. KO mice received either SP-A1, SP-A2, or both. AM were collected and their proteomes examined with 2D-DIGE. 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 more changes occurred in the oxidative stress, protease/chaperones, and inflammation groups with SP-A2 treatment than with SP-A1. In females most SP-A1-induced changes were in the 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. Females are more responsive to SP-A1, whereas the gene-specific differences in males were minimal. These observations not only demonstrate the therapeutic potential of exogenous SP-A, but also illustrate sex- and gene-specific differences in the response to it.
  
  
  CONCLUSIONS
  This study shows that changes occur in the alveolar macrophage proteome in response to a single in vivo treatment with exogenous SP-A1 and/or SP-A2. We demonstrate that SP-A1 and SP-A2 have different effects on the AM proteome and that sex differences exist in the response to each SP-A1 and SP-A2 gene product. This study illustrates the potential of exogenous SP-A1 and SP-A2 treatment for the manipulation of macrophage function and indicates that the specific SP-A variant used for treatment may vary with sex and with the cellular functions being modified. The observed changes may contribute to sex differences in the incidence of some lung diseases.
authors: The Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors: David S
authors: DS
authors: Phelps
authors: The Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors: Todd M
authors: TM
authors: Umstead
authors: The Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA; Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA, USA. Electronic address: jfloros@psu.edu.
authors: Joanna
authors: J
authors: Floros
mesh_terms: D000208:Acute Disease; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology*; D012727:Sex Characteristics
chemical_list: D020543:Proteome; D037662:Pulmonary Surfactant-Associated Protein A; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human
keywords: Actin; Autophagy; Inflammation; Innate immunity; Oxidative stress; Surfactant