Effect of soluble fungal (1-->3)-beta-D-glucan obtained from Sclerotinia sclerotiorum on alveolar macrophage activation.
In this study, we examined the effect of systemic administration of SSG, a soluble highly branched (1-->3)-beta-D-glucan obtained from a fungus Sclerotinia sclerotiorum IFO 9395, on pulmonary immune responses in mice. SSG (10 mg/kg) administered intravenously (i.v.) rapidly leaked into the alveolar space and enhanced several functions of alveolar macrophages (AMs), such as phagocytic activity, lysosomal enzyme activity, active oxygen secretion and cytokine production, on day 1 post-administration. However, kinetic changes of influx of SSG into alveoli and AM activation after SSG treatment were different. The enhanced AM functions decreased to control value on day 2 when SSG still existed at the alveolar space. Additionally, a high dose (500 micrograms/ml) of SSG was needed to activate AMs in vitro. These data imply that the stimulation by SSG alone is not effective on AM activation. SSG administered i.v. also augmented interferon gamma (IFN gamma) mRNA expression in the lung tissue, and the kinetic change of the expression was similar to that of AM activation. Additionally, a synergistic effect of SSG and IFN gamma was observed on AM activation in vitro. It may be possible that IFN gamma produced by pulmonary T cells is one of the important factors for AM activation in vivo by SSG injection. Furthermore, SSG administered i.v. enhanced candidacidal activity and cytolytic activity against pulmonary metastatic Lewis lung carcinoma (3LL) cells of AMs, and inhibited significantly the experimental pulmonary metastasis of 3LL cells. These observations are very useful for the clinical application of SSG as a biological response modifier (BRM).
Sakurai
T
T
Laboratory of Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Ohno
N
N
Suzuki
I
I
Yadomae
T
T
D000818:Animals; D001203:Ascomycota; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005936:Glucans / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D007155:Immunologic Factors / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D047071:beta-Glucans
D017931:DNA Primers; D005936:Glucans; D007155:Immunologic Factors; D012333:RNA, Messenger; D047071:beta-Glucans; D007371:Interferon-gamma; C033363:beta-1,3-glucan