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Alkaline conditions accelerate polymorphonuclear leukocyte apoptosis in vitro
1Sections of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, Columbus, Ohio 43210, USA.
Infection and Immunity
|March 20, 1999
Summary
Alkaline conditions significantly increase polymorphonuclear leukocyte (PMN) apoptosis. Serine proteases and caspases appear to mediate this process, offering potential therapeutic targets.
Area of Science:
- Cellular Biology
- Immunology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMNs) play crucial roles in innate immunity.
- Apoptosis is a critical process for immune homeostasis and resolution of inflammation.
- Cellular microenvironments, including pH, can influence immune cell function and survival.
Purpose of the Study:
- To investigate the effect of varying pH conditions on PMN apoptosis.
- To explore the enzymatic pathways involved in pH-induced PMN apoptosis.
Main Methods:
- Culturing of PMNs under different pH conditions (acidic, neutral, alkaline).
- Quantification of apoptosis rates at specific time points.
- Assessment of the impact of enzyme inhibitors (serine proteases, caspase-1, caspase-3) on apoptosis.
Main Results:
- Apoptosis rates in PMNs increased significantly with increasing pH.
- At pH 8.2, apoptosis reached 60% within 3 hours.
- Inhibitors of serine proteases, caspase-1, and caspase-3 markedly reduced apoptosis at pH 8.2.
Conclusions:
- Mildly alkaline extracellular environments promote significant PMN apoptosis.
- Serine proteases, caspase-1, and caspase-3 are key mediators of alkaline-induced PMN apoptosis.
- These findings suggest novel mechanisms regulating PMN lifespan and inflammation.