title: Chitin particle-induced cell-mediated immunity is inhibited by soluble mannan: mannose receptor-mediated phagocytosis initiates IL-12 production.
abstract: Previous studies showed that mouse spleen cells produced IL-12, TNF-alpha, and IFN-gamma when stimulated with phagocytosable-size chitin particles (N-acetyl-D-glucosamine polymers). To dissect the mechanisms of the cytokine production in this study, spleen cells from BALB/c mice were cultured with 1 to 10 microm chitin particles, heat-killed Corynebacterium parvum vaccine, zymosan, and mannan (a mannose polymer)-coated latex beads (1 microm) at 1, 10, or 100 microg/ml. We found that these particles induced IL-12, TNF-alpha, and IFN-gamma. However, these cytokines were not produced when spleen cells were cultured with soluble chitin, mannan, or laminarin (a polymer of beta-glucan), 1 to 10 microm beta-glucan particles, laminarin-coated latex beads, 1 microm latex beads, 50 to 100 microm chitin particles, or 50 to 100 microm mannan-coated beads. Soluble mannan, but not soluble laminarin, inhibited cytokine production following stimulation with 1 to 10 microm chitin particles, zymosan, or heat-killed C. parvum. In addition, cytochalasin D also inhibited cytokine production. The treatments with soluble mannan or with cytochalasin D, in sharp contrast, did not inhibit LPS-induced IL-12/IFN-gamma production or exogenous IL-12-induced IFN-gamma production. Finally, spleen cells from C3H/HeJ mice also showed comparable levels of IL-12/TNF-alpha/IFN-gamma production when induced by 1 to 10 microm chitin particles. Taken together, our results indicate that mannose receptor-mediated phagocytosis, but not the receptor-mediated pinocytosis, is highly associated with the production of IFN-gamma-inducing extracellular signaling factors such as IL-12 and TNF-alpha. The novel mechanism of phagocytosis-dependent IL-12 production appears to be distinct from that of LPS-induced cytokine production.
authors.affiliation: Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shibata
authors.forename: W J
authors.initials: WJ
authors.lastname: Metzger
authors.forename: Q N
authors.initials: QN
authors.lastname: Myrvik
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002686:Chitin / Q000494:pharmacology*; D015638:Cytochalasin D / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005936:Glucans; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008351:Mannans / Q000494:pharmacology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008863:Microspheres; D010587:Phagocytosis; D010873:Pinocytosis; D011134:Polysaccharides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D012995:Solubility; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000199:Actins; D005936:Glucans; D037181:Lectins, C-Type; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D002686:Chitin; D018664:Interleukin-12; D015638:Cytochalasin D; D007371:Interferon-gamma; C008247:laminaran; D015054:Zymosan