BACKGROUND: Acute pyelonephritis is one of the most common bacterial infections. Tissue-type plasminogen activator (tPA) is a potent fibrinolytic agent, but can play a role in inflammatory processes as well. METHODS: We induced pyelonephritis in tPA(-/-) and C57BL/6 wild-type (WT) mice by intravesical inoculation with 10(10) CFU uropathogenic Escherichia coli 1677. The mice were killed after 24 and 48 h, after which bacterial outgrowth and cytokine levels in kidney homogenates were determined. Influx of neutrophils was quantified by myeloperoxidase-ELISA. Neutrophil phagocytosis and oxidative burst were measured. RESULTS: The tPA(-/-) kidneys contained significantly higher numbers of E. coli CFU, accompanied by higher levels of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). The number of infiltrating neutrophils was similar in tPA(-/-) and WT mice at both time points, suggesting that tPA(-/-) neutrophils have a lower ability to eliminate E. coli. Phagocytosis of E. coli organisms was not diminished in tPA(-/-) neutrophils. Interestingly, tPA(-/-) neutrophils showed a significantly lower ability to generate an oxidative burst reaction upon stimulation with E. coli than WT neutrophils. Incubation with recombinant tPA reversed this effect completely. CONCLUSIONS: These results show that deletion of the tPA-gene in mice leads to lower bactericidal potential of tPA(-/-) neutrophils, which results in significantly more bacterial outgrowth during experimental pyelonephritis.
BACKGROUND: Acute pyelonephritis is one of the most common bacterial infections. Tissue-type plasminogen activator (tPA) is a potent fibrinolytic agent, but can play a role in inflammatory processes as well. METHODS: We induced pyelonephritis in tPA(-/-) and C57BL/6 wild-type (WT) mice by intravesical inoculation with 10(10) CFU uropathogenic Escherichia coli 1677. The mice were killed after 24 and 48 h, after which bacterial outgrowth and cytokine levels in kidney homogenates were determined. Influx of neutrophils was quantified by myeloperoxidase-ELISA. Neutrophil phagocytosis and oxidative burst were measured. RESULTS: The tPA(-/-) kidneys contained significantly higher numbers of E. coli CFU, accompanied by higher levels of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). The number of infiltrating neutrophils was similar in tPA(-/-) and WT mice at both time points, suggesting that tPA(-/-) neutrophils have a lower ability to eliminate E. coli. Phagocytosis of E. coli organisms was not diminished in tPA(-/-) neutrophils. Interestingly, tPA(-/-) neutrophils showed a significantly lower ability to generate an oxidative burst reaction upon stimulation with E. coli than WT neutrophils. Incubation with recombinant tPA reversed this effect completely. CONCLUSIONS: These results show that deletion of the tPA-gene in mice leads to lower bactericidal potential of tPA(-/-) neutrophils, which results in significantly more bacterial outgrowth during experimental pyelonephritis.
Authors: Mark C Dessing; Loes M Butter; Gwendoline J Teske; Nike Claessen; Chris M van der Loos; Thomas Vogl; Johannes Roth; Tom van der Poll; Sandrine Florquin; Jaklien C Leemans Journal: PLoS One Date: 2010-10-14 Impact factor: 3.240
Authors: John Ketz; Vijay Saxena; Samuel Arregui; Ashley Jackson; George J Schwartz; Takafumi Yagisawa; Robert L Fairchild; David S Hains; Andrew L Schwaderer Journal: Am J Physiol Renal Physiol Date: 2020-05-11
Authors: Jenna R DiRito; Sarah A Hosgood; Melanie Reschke; Claire Albert; Laura G Bracaglia; John R Ferdinand; Benjamin J Stewart; Christopher M Edwards; Anand G Vaish; Sathia Thiru; David C Mulligan; Danielle J Haakinson; Menna R Clatworthy; W Mark Saltzman; Jordan S Pober; Michael L Nicholson; Gregory T Tietjen Journal: Am J Transplant Date: 2020-07-05 Impact factor: 8.086