title: Neutrophil-derived hyperresistinemia in severe acute streptococcal infections.
abstract: The concept of neutrophil activation and degranulation as important contributors to disease pathology in invasive group A streptococcal infections has recently been emphasized. This study focuses on two of the most severe streptococcal manifestations, toxic shock syndrome and necrotizing fasciitis, and the newly described proinflammatory molecule resistin, known to derive from adipocytes and monocytes. We demonstrate for the first time that these conditions are characterized by hyperresistinemia in circulation as well as at the local site of infection. Importantly, analyses of patient tissue biopsies and whole blood revealed that neutrophils represent a novel and dominant source of resistin in bacterial septic shock. This was confirmed by the identification of resistin within neutrophil azurophilic granules. In vitro assays using primary neutrophils showed that resistin release was readily triggered by streptococcal cell wall components and by the streptococcal M1 protein, but not by the potent streptococcal superantigens. This is the first report demonstrating that resistin is released from neutrophils in response to microbial stimuli, which adds resistin to the neutrophil granule proteins that are likely to contribute to the pathologic inflammatory responses associated with severe streptococcal infections.
authors.affiliation: Department of Medicine F59, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.forename: Anna
authors.initials: A
authors.lastname: Linnér
authors.forename: Jonas
authors.initials: J
authors.lastname: Sundén-Cullberg
authors.forename: Axana
authors.initials: A
authors.lastname: Haggar
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Treutiger
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
mesh_terms: D000208:Acute Disease; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D016022:Case-Control Studies; D019115:Fasciitis, Necrotizing / Q000209:etiology / Q000276:immunology; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D052243:Resistin / Q000097:blood*; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D052243:Resistin; C014689:streptococcal M protein