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Effect of allogeneic polymorphonuclear neutrophils on staphylococcal sepsis in mice
S Belotsky1, L Diamantstein, E Rubinstein
1Infectious Diseases Unit, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel.
Abstract:
The antibacterial and host-damaging properties of locally injected allogeneic polymorphonuclear neutrophils (PMN) were studied in vivo. Peritoneal PMN were obtained from donor mice 24 h after i.m. infection with sublethal (SD) and lethal (LD) dose of Staphylococcus aureus. These donor PMN were mixed with S. aureus and injected i.m. into normal recipient mice. Normal donor PMN and PMN obtained from SL-infected donor mice did not induce the mortality of SL-infected recipient mice but protected LD-infected recipients (5.8% mortality vs. 29.4%). PMN obtained from LD-infected donor mice caused ca. 77% mortality in SD-infected recipients. In survivors, during the first 3 h infection, serum tumor necrosis factor (TNF) concentrations were higher than those in nonsurvivors and then decreased. In contrast, TNF level in nonsurvivors continued to be increased until death. PMN from LD-infected donors had the highest spontaneous chemiluminescence response (CL), the shortest time of peak and the lowest level of intracellular CL against S. aureus. These donor PMN exhibited increased phagocytosis and decreased killing of S. aureus than that of PMN of SD-infected donor mice. Early stimulation of PMN functions such as bacterial internalization and respiratory burst may result in decrease of their tissue-damaging properties.
Insights
Polymorphonuclear neutrophils (PMN) from lethal Staphylococcus aureus infections caused high mortality in recipients. Early PMN stimulation may reduce their tissue-damaging effects, offering potential therapeutic insights.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Polymorphonuclear neutrophils (PMN) play a critical role in host defense against bacterial infections.
- The dual role of PMN, exhibiting both antibacterial and host-damaging properties, is not fully understood.
- Understanding PMN behavior in response to different infection severities is crucial for developing effective immunotherapies.
Purpose of the Study:
- To investigate the in vivo antibacterial and host-damaging properties of allogeneic PMN.
- To determine the impact of donor mouse infection severity (sublethal vs. lethal) on PMN function and recipient outcomes.
- To explore the relationship between PMN function, tumor necrosis factor (TNF) levels, and mortality in Staphylococcus aureus infection models.
Main Methods:
- Isolation of peritoneal PMN from mice infected with sublethal (SD) or lethal (LD) doses of Staphylococcus aureus.
- Intramuscular injection of donor PMN (alone or mixed with S. aureus) into normal recipient mice.
- Assessment of recipient mortality, serum TNF concentrations, and PMN functions including chemiluminescence (CL), phagocytosis, and bacterial killing.
Main Results:
- PMN from LD-infected donors induced high mortality (77%) in SD-infected recipients.
- PMN from SD-infected donors protected LD-infected recipients (5.8% mortality vs. 29.4%).
- LD-donor PMN showed increased phagocytosis but decreased killing of S. aureus, with altered chemiluminescence responses.
Conclusions:
- PMN derived from lethal infections possess heightened host-damaging properties.
- Early stimulation of PMN functions like bacterial internalization and respiratory burst may mitigate their tissue-damaging potential.
- Modulating PMN function represents a potential therapeutic strategy for bacterial infections.