engleski

Mouse model of experimental asthma using (1-3)-beta-D- glucan derivatives

Rationale: (1-3)-beta-D-Glucans are fungal cell wall polysaccharides that stimulate innate immune responses and are responsible for bioaerosol-induced respiratory symptoms in both indoor and occupational environments. Methods: C3HeB/FeJ mice were exposed by inhalation to two different glucan compounds after testing their configuration by NMR methods: scleroglucan, a (1-3)(1-6)-branched glucan and curdlan, a linear (1-3) glucan. Negative control mice were exposed to saline or alum. At day 0, mice received I.P. injection of BSA-glucan conjugates with alum. The negative control group received injected alum in saline (control A), or saline alone (control B). At day 14-16, 21-23, and 28-30 mice were challenged intranasally (I.N.) with glucan (25ug/mouse) and negative control mice received saline. At day 31euthanasia and exsanguinations were performed. We analyzed total and differential cells, INF-gamma, TNF-alpha in bronchoalveolar lavage fluid (BALF) and total serum IgE (sIgE). Results: Total BALF cells were significantly higher in scleroglucan-treated than in curdlan-treated mice or either control group. No difference was found between curdlan and mice injected with alum. The proportion of macrophages was decreased in mice treated with curdlan. Total IgE was higher in scleroglucan or cudlan vs. control groups. No difference in IgE level was found between scleroglucan and curdlan groups. Interferon was elevated in glucan treated animals over controls. Exposure Groups Mean ± S.E. BAL Cells/mouse (1000s) % Monocytes IFNγ , pg/mL IgE, ng/mL Saline Inj., Saline Inh. 72 ± 16.6 93.4 72.6 ± 35.5 907 Alum Inj., Saline Inh. 152 ± 6.7 95.1 68.0 ± 12.4 417 Curdlan Inj. & Inh. 117.5 ± 19.5 69.6 203.4 ± 33.8 1600 Scleroglucan Inj. & Inh. 183.1 ± 18.6 90.8 181.6 ± 38.4 1590 Conclusion: This study shows that the branching pattern of inhaled glucans is an important determinant of their inflammatory potency and immunogenicity. Funded by: U.I. Center for Health Effects of Environmental Contamination

mouse; glucan; respiratory symptoms

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