Different role of serum components and cytokines on alveolar macrophage activation by soluble fungal (1-->3)-beta-D-glucan.
In this study, we investigated the mechanism of alveolar macrophage activation by systemic administration of SSG, a soluble highly branched (1-->3)-beta-D-glucan obtained from a fungus Sclerotinia sclerotiorum IFO 9395. Multiple i.v. administration (10 mg/kg; once daily for 10 consecutive days) of SSG enhanced some functions of alveolar macrophages, such as lysosomal enzyme activity and nitric oxide secretion, on day 1 after the last administration, and it also elevated the concentrations of serum protein, interferon gamma and SSG in bronchoalveolar lavage fluid on the same day. On the in vitro assay system, stimulation by SSG alone (500 microg/ml) slightly augmented the lysosomal enzyme activity of alveolar macrophages, but it had no effect on nitric oxide production of cells. Stimulation by serum (1 or 10% mouse serum) or serum components, such as fibronectin (25 microg/ml) and albumin (500 microg/ml), alone strongly augmented only the lysosomal enzyme activity of alveolar macrophages, but it had no effect on nitric oxide secretion from cells, and no synergism or additive-like effect was observed between serum components and SSG. In contrast, stimulation by crude lymphokine (5%) or recombinant murine interferon gamma (100 U/ml) alone did not induce augmentation of lysosomal enzyme activity and nitric oxide production of alveolar macrophages in vitro, but when cells were incubated together with crude lymphokine or recombinant murine interferon gamma and SSG (500 microg/ml), a significant combined effect was observed on both functions of alveolar macrophages. In addition, pretreatment of crude lymphokine or recombinant murine interferon gamma enhanced the expression of beta-D-glucan specific binding sites on the alveolar macrophage surface in vitro though pretreatment by serum components had no effect. Based on these findings, the enhancement of alveolar macrophage functions by systemic administration of SSG appears to be mediated, at least in part, by both the simple effect of serum components including fibronectin and albumin leaked from pulmonary peripheral blood into the alveoli and the synergistic effect between lymphokines released from activated pulmonary T cells and SSG itself entering the alveoli after SSG injection via the priming effect of lymphokines which enhances the expression of beta-D-glucan specific binding sites on the alveolar macrophage surface.
Sakurai
T
T
Laboratory of Environmental Chemistry, School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. sakurai@ls.toyaku.ac.jp
Kaise
T
T
Yadomae
T
T
Matsubara
C
C
D000818:Animals; D001203:Ascomycota; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005353:Fibronectins / Q000378:metabolism; D005936:Glucans / Q000378:metabolism / Q000494:pharmacology*; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology*; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D047071:beta-Glucans
D005353:Fibronectins; D005936:Glucans; D007155:Immunologic Factors; D008222:Lymphokines; D012709:Serum Albumin; D047071:beta-Glucans; D009569:Nitric Oxide; C033363:beta-1,3-glucan