Propionic acid-induced calcium mobilization in human neutrophils

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Cytoplasmic free calcium (Ca2+) is a critical second messenger in cellular signaling.
• Neutrophils play a key role in the innate immune response.

Purpose of the Study:

• To investigate the effect of propionic acid on intracellular calcium levels in human neutrophils.
• To elucidate the signaling pathways involved in propionic acid-induced calcium mobilization.

Main Methods:

• Human neutrophils were treated with propionic acid, and cytoplasmic Ca2+ levels were measured.
• Pertussis toxin and cholera toxin were used to assess the involvement of G-proteins.
• Phorbol 12-myristate 13-acetate (PMA) and H-7 were used to investigate the role of protein kinase C (PKC).
• Synthetic chemotactic factors and their antagonists were employed to study cross-talk with other signaling pathways.

Main Results:

• Propionic acid induced a rapid, dose-dependent increase in cytoplasmic Ca2+ in neutrophils, utilizing both intracellular and extracellular calcium stores.
• The calcium mobilization was inhibited by pertussis toxin, suggesting the involvement of a guanine nucleotide-binding protein (G-protein).
• PMA pre-treatment reduced the calcium response, an effect reversed by the PKC inhibitor H-7.
• Pre-incubation with fMet-Leu-Phe reduced the propionic acid-induced calcium transient, but other antagonists had no effect.
• Propionic acid did not affect calcium levels in monocytes, lymphocytes, or platelets, but induced a response in differentiated HL-60 cells.

Conclusions:

• Propionic acid is a potent stimulator of calcium mobilization in human neutrophils through a G-protein-dependent pathway.
• Protein kinase C signaling modulates the neutrophil response to propionic acid.
• The findings suggest a specific role for propionic acid in neutrophil activation, with potential implications for immune responses.