Changes in immune mediators in mouse lung produced by administration of soluble (1-->3)-beta-D-glucan.
In this study, we showed that systemic administration of SSG, a highly branched soluble (1-->3)-beta-D-glucan obtained from Sclerotinia sclerotiorum, induced immunological changes in the alveolar space of mice in vivo, assessed by analysing some immune mediators in bronchoalveolar lavage (BAL) fluid. A single i.v. administration of SSG (250 micrograms/mouse) induced a rapid but transient leakage of the serum components, IgG and fibronectin, into the alveolar space. This was apparent 12 h post-administration and reached a peak on day 2. Similar kinetic changes were found for lysosomal enzyme activities and interferon gamma (IFN gamma) concentrations in BAL which are markers of activated alveolar macrophages (AMs) or pulmonary T cells. BAL prepared from SSG-treated mice stimulated lysosomal enzyme release from AMs in vitro. However, SSG did not provoke the chronic accumulation of serum proteins in alveoli and did not induce the release of detectable amounts of nitric oxide and the inflammatory cytokines, IL-1, IL-6 and TNF alpha, into BAL. However, their mRNAs were detected in lung tissue using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique. Similar results were observed for multiple i.v. administration (250 micrograms, once a day for 10 consecutive days), and there were a little differences between single and multiple administration. In summary, systemic administration of SSG induces immune responses, including activation of AMs and lymphocytes, but does not provoke chronic inflammation in the alveolar space when administered either as single or multiple doses. This finding is very important for the clinical application of SSG in immunocompromised hosts as a biological response modifier (BRM) without toxic-side effects on lung tissue.
Sakurai
T
T
Laboratory of Immunopharmacology of Microbial Products, Tokyo College of Pharmacy, Japan.
Ohno
N
N
Yadomae
T
T
D000818:Animals; D001203:Ascomycota / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005936:Glucans / Q000302:isolation & purification / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000378:metabolism; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D047071:beta-Glucans
D016207:Cytokines; D005353:Fibronectins; D005936:Glucans; D007074:Immunoglobulin G; D007155:Immunologic Factors; D011506:Proteins; D012333:RNA, Messenger; D047071:beta-Glucans; D009569:Nitric Oxide; C033363:beta-1,3-glucan