TY - JOUR
T1 - Neutrophil-Derived Hyperresistinemia in Severe Acute Streptococcal Infections
AU - Johansson, Linda
AU - Linner, Anna
AU - Sunden-Cullberg, Jonas
AU - Haggar, Axana
AU - Herwald, Heiko
AU - Lore, Karin
AU - Treutiger, Carl-Johan
AU - Norrby-Teglund, Anna
PY - 2009
Y1 - 2009
N2 - 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. The Journal of Immunology, 2009, 183: 4047-4054.
AB - 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. The Journal of Immunology, 2009, 183: 4047-4054.
U2 - 10.4049/jimmunol.0901541
DO - 10.4049/jimmunol.0901541
M3 - Article
C2 - 19717514
SN - 1550-6606
VL - 183
SP - 4047
EP - 4054
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -