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Isolation, Purification and Labeling of Mouse Bone Marrow Neutrophils for Functional Studies and Adoptive Transfer Experiments
Published on: July 10, 2013
Studies on polymorphonuclear leukocyte bactericidal function: the role of exogenous cytokines
1Brown University School of Medicine, Division of Surgical Research, Rhode Island Hospital, Providence 02903, USA.
Shock (Augusta, Ga.)
|February 1, 1997
Summary
Exogenous cytokines like IL-8, TNF-alpha, and IL-1 beta enhance polymorphonuclear neutrophil (PMN) killing of bacteria. These cytokines, particularly TNF-alpha and IL-1 beta, maintain PMN bactericidal activity at low cell ratios.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are crucial for innate immunity.
- Bacterial infections pose a significant health challenge.
- The role of exogenous cytokines in modulating PMN function requires further elucidation.
Purpose of the Study:
- To investigate the impact of exogenous interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and IL-1 beta on PMN bactericidal activity.
- To determine the effects of varying PMN:bacterial target ratios and cytokine concentrations on PMN function.
- To explore the mechanisms underlying cytokine-mediated enhancement of PMN bactericidal activity.
Main Methods:
- Assessing PMN bactericidal activity against Staphylococcus aureus and Escherichia coli over time.
- Evaluating the influence of different PMN:target ratios (20:1 to 5:1) on bacterial killing.
- Conducting dose-response studies with physiologically relevant cytokine concentrations.
- Utilizing monoclonal antibodies to block cytokine receptors and assessing the oxidative burst pathway.
Main Results:
- Exogenous cytokines, particularly TNF-alpha and IL-1 beta, preserved PMN bactericidal activity against E. coli and S. aureus, especially at lower PMN:target ratios.
- Cytokine-induced enhancement of bactericidal activity was observed at physiologically relevant concentrations.
- Blocking cytokine receptors or inhibiting the terminal oxidative burst significantly reduced the beneficial effects of cytokines.
- IL-8 and TNF-alpha showed time-dependent effects on PMN activity against E. coli.
Conclusions:
- Individual cytokines at low concentrations significantly enhance PMN bactericidal activity through oxidant-dependent mechanisms.
- TNF-alpha and IL-1 beta are particularly effective in maintaining PMN function under challenging conditions (low PMN:target ratios).
- Targeting cytokine functions at infectious sites may not always be beneficial due to their role in enhancing PMN activity.
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