| Abstrakt: |
Oral vomitoxin (VT) exposure in mice results in elevated cytokine gene expression, increased production of IgA, and IgA nephropathy. To determine the potential role of macrophages (Mφ) in these effects, anex vivomodel was devised whereby Peyer's patch (PP) and spleen cells were prepared from mice 2 h after oral exposure to 0 or 25 mg/kg body wt VT, cultured, and then evaluated for IgA and cytokine IL-6 production. Both PP and, to a lesser extent, spleen cells from treatment mice produced more IgA over a 7-day period than did corresponding control cells when cultured without a costimulus or in the presence of either phorbol myristate acetate plus ionomycin (PMA + ION) or lipopolysaccharide (LPS); IgA elevation was most marked in LPS-treated cultures. The VT effect was completely ablated in PP cultures that were depleted of Mφ but not in Mφ-depleted spleen cultures. VT exposure similarly increased production of IL-6, an important helper factor for IgA secretion, in LPS-stimulated PP and spleen cell cultures. IL-6 production was also ablated by Mφ depletion. A potential costimulatory role for Mφ was further suggested because both IgA and IL-6 production increased when Mφ-depleted PP cells from VT-treated animals were cocultured with peritoneal Mφ from VT-treated animals. Similar effects were observed when an analogousex vivoapproach was used with purified PP B cells and peritoneal Mφ. PP B cells from control animals also secreted elevated levels of IgA when cocultured with splenic CD4+cells from VT-treated animals, thus confirming previous studies showing that T cell help also contributes to increased IgA production. Potential roles for soluble mediators and cell contact in this process were suggested when IgA production was measured in cultures of PP cells separated from VT-treated Mφ by a semipermeable membrane. Taken together, these and previous results suggest that Mφ may play a key mechanistic role in elevated IgA production and IgA nephropathy in VT-exposed mice. |
Full Text from ScienceDirect