PROPIONIC ACID STIMULATES SUPEROXIDE GENERATION IN HUMAN NEUTROPHILS

✍ Scribed by SUMI NAKAO; YOSHIKO MORIYA; SHUNSUKE FURUYAMA; RICHARD NIEDERMAN; HIROSHI SUGIYA

• Publisher: Elsevier Science
• Year: 1998
• Tongue: English
• Weight: 235 KB
• Volume: 22
• Category: Article
• ISSN: 1065-6995
• DOI: 10.1006/cbir.1998.0263

✦ Synopsis

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca 2+ ([Ca 2+ ] i ) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 m) induced inositol 1,4,5-trisphosphate (IP 3 ) formation and a rapidly transient increase in [Ca 2+ ] i , but not superoxide generation, whereas 1  formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophilstimulating bacterial peptide, stimulated not only IP 3 formation and Ca 2+ mobilization but also superoxide generation. The IP 3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca 2+ ] i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca 2+ ] i , which was higher than the basal level, following a transient increase in [Ca 2+ ] i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca 2+ , thapsigargin, a potent inhibitor of endoplasmic reticulum Ca 2+ -ATPase, induced an increase in [Ca 2+ ] i even after propionic acid stimulation, but not after fMLP. The Ca 2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca 2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca 2+ ionophore and a Ca 2+ influx activator.