Effects of particulate and soluble (1–3)-β-glucans on Ca2+ influx in NR8383 alveolar macrophages

• Published in: Immunopharmacology 1998-07, Vol.40 (1), p.77-89
• Main Authors: Mörk, Ann-Christin, Helmke, Ronald J, Martinez, J.Ricardo, Michalek, Michael T, Patchen, Myra L, Zhang, Guo H
• Format: Article
• Language: English
• Subjects: (1–3)-β-glucans; Adjuvants, Immunologic - pharmacology; Animals; Anti-Infective Agents - pharmacology; beta-Glucans; Biological and medical sciences; Ca2+ influx; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Cell Line; Cell physiology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Glucans - chemistry; Glucans - pharmacology; Immunologic Factors - pharmacology; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Molecular and cellular biology; Molecular Weight; NR8383 alveolar macrophages; Particle Size; Phagocytosis; Rats; Receptors, Immunologic - metabolism; Saccharomyces cerevisiae; Signal transduction; Solubility; Zymosan - pharmacology
• ISSN: 0162-3109
• DOI: 10.1016/S0162-3109(98)00033-2

Particulate and soluble (1–3)-β-glucans are effective in preventing infections by enhancing macrophage and neutrophil functions. However, the mechanisms triggering these enhanced cellular responses are essentially unknown. We recently demonstrated that zymosan, a particulate (1–3)-β-glucan receptor agonist, caused an influx of Ca2+ in NR8383 rat alveolar macrophages (AMs) and a resulting increase in intracellular Ca2+ (Zhang et al., J. Leukoc. Biol. 62 (1997) 341–348). Since Ca2+ is important in mediating leukocyte responses, we investigated whether other (1–3)-β-glucans also alter Ca2+ mobilization in AMs. Particulate and soluble (1–3)-β-glucans derived from Saccharomyces cerevisiae were used in these studies. Like zymosan, particulate (1–3)-β-glucan (WGPs) caused a concentration-dependent increase in [Ca2+]i, which was inhibited by removal of extracellular Ca2+ and by SKF96365, an inhibitor of receptor-operated Ca2+ channels. When three different soluble (1–3)-β-glucans, with molecular weights of approximately 11,000, 150,000, and 1,000,000 Da, were tested alone for effects on Ca2+ responses, the low molecular weight (1–3)-β-glucan produced no effect and the intermediate and high molecular weight (1–3)-β-glucans caused only a small increase in [Ca2+]i. Interestingly, however, all three soluble (1–3)-β-glucans could significantly reduce the Ca2+ responses induced by a subsequent exposure to either WGPs or zymosan. These results demonstrate that: 1) particulate (1–3)-β-glucan activates Ca2+ influx in NR8383 macrophages through receptor-operated Ca2+ channels; 2) soluble (1–3)-β-glucans do not strongly activate Ca2+ influx in these cells; and 3) soluble (1–3)-β-glucans significantly inhibit Ca2+ influx induced by WGPs or zymosan. Soluble (1–3)-β-glucans are likely to prevent Ca2+ influx by competitively binding to the (1–3)-β-glucan receptors recognizing zymosan and WGPs. The smaller Ca2+ influx induced by soluble (1–3)-β-glucans may represent only a partial activation of post-receptor signal transduction pathways necessary for inducing Ca2+ influx.