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Extracellular acidification induces human neutrophil activation
A S Trevani1, G Andonegui, M Giordano
1Laboratory of Immunology, Institute of Hematologic Research, National Academy of Medicine, Buenos Aires University School of Medicine, Argentina. neu@connmed.com.ar
Journal of Immunology (Baltimore, Md. : 1950)
|April 14, 1999
Summary
Extracellular acidosis activates neutrophils, enhancing their inflammatory response and prolonging their lifespan. This occurs through increased intracellular calcium and CD18 expression, even delaying apoptosis.
Area of Science:
- Immunology
- Cell Physiology
Background:
- Neutrophils play a critical role in acute inflammation.
- The impact of extracellular pH on neutrophil function is not fully understood.
Purpose of the Study:
- To investigate the effects of extracellular acidification on neutrophil physiology and function.
- To determine if extracellular acidosis modulates neutrophil activation and apoptosis.
Main Methods:
- Neutrophils were suspended in bicarbonate-buffered RPMI 1640 medium at acidic pH (6.5-7.0).
- Intracellular calcium levels, forward light scattering, and CD18 expression were measured.
- Hydrogen peroxide production and myeloperoxidase release were assessed.
- Neutrophil responses to agonists (FMLP, immune complexes, opsonized zymosan) were evaluated under acidic conditions.
- Neutrophil apoptosis and intracellular pH changes were monitored.
Main Results:
- Extracellular acidification caused a rapid increase in intracellular calcium, enhanced forward light scattering, and upregulated CD18 expression.
- Acidosis alone did not induce H2O2 production or MPO release but significantly enhanced these responses when neutrophils were stimulated with agonists.
- Acidic extracellular pH delayed neutrophil apoptosis and extended their functional lifespan.
- Extracellular acidification led to an immediate and sustained drop in intracellular pH in bicarbonate-buffered solutions.
Conclusions:
- Extracellular acidosis activates neutrophils, intensifying inflammatory responses.
- Acidosis delays neutrophil apoptosis, extending their functional lifespan.
- Intracellular acidification appears to play a role in neutrophil activation by extracellular acidosis.