title: The role of Serpine-1 and Tissue inhibitor of metalloproteinase type-1 in early host responses to Staphylococcus aureus intracutaneous infection of mice.
abstract: Staphylococcus aureus is a common cause of skin and soft tissue infections in animal and humans. In the current study, we hypothesized that early host responses to S. aureus infection leading to the recruitment of neutrophils and control of the bacterium at the site of infection depend on the expression of Serpine-1 and Tissue inhibitor of metalloproteinase type-1, two important endogenous proteinase inhibitors that possess regulatory properties on a variety of pathophysiological conditions. Using a mouse model of skin infection and single-gene and double-gene knockout mice, however, our observations showed that Serpine-1 and Tissue inhibitor of metalloprotease type-1 did not impact the number of bacteria accumulating at the site of infection. Double-gene knockout mice further had the same volume of accumulating host cells at the site of infection, while single Tissue inhibitor of metalloprotease type-1 knockout mice showed a decreased number of cells. Follow-up studies demonstrated changes in Serpine-1, Tissue inhibitor of metalloprotease type-1 and IL-6 plasma levels following challenge. In addition, double-gene knockout mice did not differ from wild-type mice in white blood cell, granulocyte and leucocyte counts, while single-gene genotypes differed in these phenotypes.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Harslund
authors.forename: Dorte
authors.initials: D
authors.lastname: Frees
authors.forename: Páll S
authors.initials: PS
authors.lastname: Leifsson
authors.forename: Hanne
authors.initials: H
authors.lastname: Offenberg
authors.forename: Maria U
authors.initials: MU
authors.lastname: Rømer
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: John E
authors.initials: JE
authors.lastname: Olsen
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D012867:Skin / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D013207:Staphylococcal Skin Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D000097522:Neuroserpin
chemical_list: D009479:Neuropeptides; D015843:Serpins; D019715:Tissue Inhibitor of Metalloproteinase-1; D000097522:Neuroserpin; C560825:Timp1 protein, mouse
keywords: Serpine-1; Tissue inhibitor of metalloprotease type-1; host response; neutrophil recruitment