Harmful and Protective Roles of Neutrophils in Sepsis

Hoesel, Laszlo M.; Neff, Thomas; Neff, Simona B; Younger, John G.; Olle, Eric W.; Gao, Hongwei; Pianko, Matthew J.; Bernacki, Kurt D.; Sarma, J. Vidya; Ward, Peter A.

doi:10.1097/01.shk.0000170353.80318.d5

Cited by 130 publications

(98 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…from neutrophils and the subsequent degradation of ECM are believed to be key factors contributing to multiple organ failure (46). Elegant studies conducted by Bosio et al (47), further support the notion that neutrophils play a key pathogenic role in mediating host susceptibility to F. tularensis LVS insofar as B cell-deficient mice succumb to infection more readily than their wild-type counterparts.…”

Section: Discussionmentioning

confidence: 64%

Matrix Metalloproteinase 9 Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B Strains of Francisella tularensis

Malik

Bakshi

McCabe

et al. 2007

The Journal of Immunology

102

113

View full text Add to dashboard Cite

A striking feature of pulmonary infection with the Gram-negative intracellular bacterium Francisella tularensis, a category A biological threat agent, is an intense accumulation of inflammatory cells, particularly neutrophils and macrophages, at sites of bacterial replication. Given the essential role played by host matrix metalloproteinases (MMPs) in modulating leukocyte recruitment and the potentially indiscriminate destructive capacity of these cells, we investigated whether MMP-9, an important member of this protease family released by neutrophils and activated macrophages, plays a role in the pathogenesis of respiratory tularemia. We found that F. tularensis induced expression of MMP-9 in FVB/NJ mice and that the action of this protease is associated with higher bacterial burdens in pulmonary and extrapulmonary tissues, development of more extensive histopathology predominated by neutrophils, and increased morbidity and mortality compared with mice lacking MMP-9 (MMP-9−/−). Moreover, MMP-9−/− mice were able to resolve infection with either the virulence-attenuated type B (live vaccine strain) or the highly virulent type A (SchuS4) strain of F. tularensis. Disease resolution was accompanied by diminished leukocyte recruitment and reductions in both bacterial burden and proinflammatory cytokine production. Notably, neutrophilic infiltrates were significantly reduced in MMP-9−/− mice, owing perhaps to limited release of Pro-Gly-Pro, a potent neutrophil chemotactic tripeptide released from extracellular matrix through the action of MMP-9. Collectively, these results suggest that MMP-9 activity plays a central role in modulating the clinical course and severity of respiratory tularemia and identifies MMPs as novel targets for therapeutic intervention as a means of modulating neutrophil recruitment.

show abstract

Section: Discussionmentioning

confidence: 64%

Matrix Metalloproteinase 9 Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B Strains of Francisella tularensis

Malik

Bakshi

McCabe

et al. 2007

The Journal of Immunology

102

113

View full text Add to dashboard Cite

show abstract

“…It has been already shown that plasma red-ox status correlates to severity scores in critically ill patients in intensive care unit [21][22][23]. Several researchers have also reported that ROS increases in severe sepsis both in patients and animal models, compared with non-critical sepsis or controls, respectively.…”

Section: Discussionmentioning

confidence: 98%

Oxidative Stress as Marker of Sepsis in Onco Hematological Patients: A Pilot Study

A¹,

C²

2015

J Blood Disord Transfus

View full text Add to dashboard Cite

show abstract

“…Thus, even though C57BL/6-Kit W-sh/W-sh mice had significantly more neutrophils in the blood, bone marrow and spleen at baseline than did the corresponding wild-type mice (Supplemental Figure 2), when tested 18 to 24 hours after the induction of moderately severe or severe CLP, the levels of intraperitoneal neutrophils or TNF were quite similar in C57BL/6-Kit It has been proposed that neutrophils can express opposing roles during CLP and other innate immune response to bacterial infection, promoting bacterial clearance but, in severe infections, also contributing to organ damage. 37 However, C57BL/6-Kit W-sh/W-sh mice engrafted with wild-type versus TNF-deficient mast cells may not differ only in the levels of TNF ( Figure 2C) and neutrophils ( Figure 2B) observed after severe CLP, but also in other mediators produced in this setting, which may be influenced by TNF and/or neutrophils. Proving which of these factors contribute most to lethality in this setting may be difficult.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Piliponsky

Chen

Grimbaldeston

et al. 2010

The American Journal of Pathology

130

174

View full text Add to dashboard Cite

We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit W-sh/W-sh mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F 1 -Kit W/W-v mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit W-sh/W-sh mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F 1 -Kit W-sh/W-sh mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast celldeficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection), mast cells can have either no detectable effect or opposite effects on survival during bacterial infections, eg, promoting survival during moderately severe CLP associated with low mortality but, in C57BL/ 6-Kit W-sh/W-sh mice, increasing mortality during severe CLP or infection with S. typhimurium. (Am J Pathol

show abstract

Harmful and Protective Roles of Neutrophils in Sepsis

Cited by 130 publications

References 42 publications

Matrix Metalloproteinase 9 Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B Strains of Francisella tularensis

Matrix Metalloproteinase 9 Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B Strains of Francisella tularensis

Oxidative Stress as Marker of Sepsis in Onco Hematological Patients: A Pilot Study

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Contact Info

Product

Resources

About