Role of macrophages in elevated IgA and IL-6 production by Peyer's patch cultures following acute oral vomitoxin exposure

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 (M phi) in these effects, an ex vivo model 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 M phi but not in M phi-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 M phi depletion, A potential costimulatory role for M phi was further suggested because both IgA and IL-6 production increased when M phi-depleted PP cells from VT-treated animals were cocultured with peritoneal M phi from VT-treated animals, Similar effects were observed when an analogous ex vivo approach was used with purified PP B cells and peritoneal M phi. 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 M phi by a semipermeable membrane, Taken together, these and previous results suggest that M phi may play a key mechanistic role in elevated IgA production and IgA nephropathy in VT-exposed mice. (C) 1998 Academic Press.