Related Experiment Videos
Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products
F Colotta1, F Re, N Polentarutti
1Istituto di Ricerche Farmacologiche Mario Negri, Centro Daniela e Catullo Borgomainerio, Milano, Italy.
Abstract:
Mature circulating polymorphonuclear cells (PMN) have the shortest half-life among leukocytes and undergo rapid programmed cell death in vitro. In this study, we have examined the possibility that inflammatory signals (cytokines and bacterial products) can regulate PMN survival. PMN in culture were found to rapidly die, with percentages of survival at 24, 48, 72, and 96 hours of 97.3% +/- 1.9%, 36.8% +/- 5.3%, 14.5% +/- 3.1%, and 4.2% +/- 2.9%, respectively (mean +/- SE of 20 different donors). PMN incubated with interleukin-1 beta (IL-1 beta), tumor necrosis factor, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and interferon-gamma (IFN-gamma), but not with prototypic chemoattractants (fMLP, recombinant C5a, and IL-8), showed a marked increase in survival, with values ranging at 72 hours of incubation from 89.5% +/- 5.8% for IL-1 beta to 47.6% +/- 6.4% for IFN-gamma. The calculated half-life was 35 hours for untreated and 115 hours for IL-1-treated PMN. PMN activated with lipopolysaccharide (LPS) or inactivated streptococci also showed a longer survival compared with untreated cells (94.4% +/- 3.2% and 95.5% +/- 2.4%, respectively, at 72 hours). PMN surviving in response to LPS or IL-1 beta retained the capacity to produce superoxide anion when treated with phorbol esters or fMLP. All inducers of PMN survival protect these cells from programmed cell death because they reduced cells with morphologic features of apoptosis and the fragmentation of DNA in multiples of 180 bp. Thus, certain cytokines and bacterial products can prolong PMN survival by interfering with the physiologic process of apoptosis. Prolongation of survival may be important for the regulation of host resistance and inflammation, and may represent a crucial permissive step for certain cytokines and microbial products that activate gene expression and function in PMN.
Insights
Inflammatory signals like cytokines and bacterial products significantly extend the survival of polymorphonuclear cells (PMN) by inhibiting programmed cell death (apoptosis). This prolonged PMN survival is crucial for regulating host resistance and inflammation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Mature polymorphonuclear cells (PMN) have a short lifespan and undergo rapid programmed cell death in vitro.
- Understanding factors that regulate PMN survival is critical for immune response and inflammation.
Purpose of the Study:
- To investigate whether inflammatory signals, including cytokines and bacterial products, can modulate PMN survival.
- To determine the impact of specific inflammatory mediators on PMN lifespan and apoptosis.
Main Methods:
- Cultured human PMN were treated with various cytokines (IL-1β, TNF, CSFs, IFN-γ) and bacterial products (LPS, inactivated streptococci).
- PMN survival rates were assessed at 24, 48, 72, and 96 hours.
- Apoptosis markers, including DNA fragmentation, were analyzed to confirm the mechanism of survival regulation.
Main Results:
- Cytokines (IL-1β, TNF, CSFs, IFN-γ) and bacterial products (LPS, streptococci) significantly increased PMN survival compared to untreated controls.
- Half-life of untreated PMN was 35 hours, extended to 115 hours with IL-1β treatment.
- Surviving PMN retained functional capacity, such as superoxide anion production.
- All tested inducers inhibited apoptosis, evidenced by reduced morphologic apoptotic features and DNA fragmentation.
Conclusions:
- Specific cytokines and bacterial products prolong PMN survival by actively inhibiting apoptosis.
- This extended PMN lifespan plays a significant role in host defense and inflammatory processes.
- Prolonged PMN survival may be a prerequisite for the action of certain immune-modulating microbial products.