Regulation of (1-3)-β-glucan-stimulated Ca2+ influx by protein kinase C in NR8383 alveolar macrophages

✍ Scribed by Ann-Christin Mörk; Xiuhua Sun; Xiao-bing Liu; Denise Rodriguez; J. Ricardo Martinez; Robert Castro; Guo H. Zhang

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 178 KB
• Volume: 78
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(20000701)78:1<131::aid-jcb12>3.0.co;2-x

✦ Synopsis

Stimulation of (1-3)-beta-glucan receptors results in Ca(2+) influx through receptor-operated channels in alveolar macrophages (AMs), but the mechanism(s) regulating Ca(2+) influx is still undefined. In this study we investigated the role of protein kinase C (PKC) regulation of Ca(2+) influx in the NR8383 AM cell line using the particulate (1-3)-beta-glucan receptor agonist zymosan. PKC inhibition with calphostin C (CC) or bisindolymaleimide I (BSM) significantly reduced zymosan-induced Ca(2+) influx, whereas activation of PKC with phorbol-12-myristate 13-acetate (PMA) or 1, 2-dioctanoyl-sn-glycerol (DOG) mimicked zymosan, inducing a concentration-dependent Ca(2+) influx. This influx was dependent on extracellular Ca(2+) and inhibited by the receptor-operated Ca(2+) channel blocker SK&F96365, indicating that zymosan and PKC activate Ca(2+) influx through a similar pathway. NR8383 AMs expressed one new PKC isoform (delta) and two atypical PKC isoforms (iota and lambda), but conventional PKC isoforms were not present. Stimulation with zymosan resulted in a translocation of PKC-delta from the cytosol to the membrane fraction. Furthermore, inhibition of protein tyrosine kinases (PTKs) with genistein prevented zymosan-stimulated Ca(2+) influx and PKC-delta translocation. These results suggest that PKC-delta plays a critical role in regulating (1-3)-beta-glucan receptor activated Ca(2+) influx in NR8383 AMs and PKC-delta translocation is possibly dependent on PTK activity.