title: S100A4 deficiency is associated with efficient bacterial clearance and protects against joint destruction during Staphylococcal infection.
abstract: BACKGROUND
  Efficient host defense mechanisms are crucial for survival in sepsis and septic arthritis. S100 proteins are reported to have proinflammatory and bactericidal properties. The aim of this study was to investigate the role of S100A4 in staphylococcal arthritis.
  
  
  METHODS
  S100A4 knockout mice (S100A4KO) and wild-type counterparts (WT) were intravenously and intra-articularly challenged with Staphylococcus aureus strain LS-1. Clinical and morphological signs of arthritis and sepsis, phagocytosis, bone mineral density (BMD), and bone metabolism were then monitored in S100A4 and WT mice.
  
  
  RESULTS
  S100A4KO mice had a lower bacterial load in the kidneys than WT mice (P < .05) but developed more severe clinical signs of arthritis (P < .001) and had higher levels of interleukin 6 and L-selectin (P = .002). S100A4KO mice had fewer morphological signs of synovitis and cartilage/bone destruction following intra-articular instillation of bacteria. S100A4KO mice were protected from loss of BMD and had lower levels of RANKL, MMP3, and MMP9 (P < .05). S100A4 was not bactericidal in vitro.
  
  
  CONCLUSIONS
  In staphylococcal infection, S100A4 regulates bacterial clearance as well as systemic and local inflammatory responses.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Denmark. li.bian@rheuma.gu.se
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Paulina
authors.initials: P
authors.lastname: Strzyz
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Malin
authors.initials: M
authors.lastname: Erlandsson
authors.forename: Annelie
authors.initials: A
authors.lastname: Hellvard
authors.forename: Mikael
authors.initials: M
authors.lastname: Brisslert
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Noona
authors.initials: N
authors.lastname: Ambartsumian
authors.forename: Mariam
authors.initials: M
authors.lastname: Grigorian
authors.forename: Maria
authors.initials: M
authors.lastname: Bokarewa
mesh_terms: D000818:Animals; D001170:Arthritis, Infectious / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D058491:Bacterial Load; D015519:Bone Density; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002357:Cartilage Diseases / Q000382:microbiology / Q000473:pathology*; D002358:Cartilage, Articular / Q000382:microbiology / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000382:microbiology; D007719:Knee Joint / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D019041:L-Selectin / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D053245:RANK Ligand / Q000097:blood; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000172:deficiency* / Q000502:physiology; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000378:metabolism / Q000473:pathology*; D013585:Synovitis / Q000382:microbiology / Q000473:pathology*
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D015850:Interleukin-6; D053245:RANK Ligand; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C505689:Tnfsf11 protein, mouse; D019041:L-Selectin; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9