ROLE OF MACROPHAGES IN ELEVATED IGA AND IL-6 PRODUCTION BY PEYERS 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 dete rmine the potential role of macrophages (M phi) in these effects, an e x vivo model was devised whereby Peyer's patch (PP) and spleen cells w ere prepared from mice 2 h after oral exposure to 0 or 25 mg/kg body w t VT, cultured, and then evaluated for IgA and cytokine IL-6 productio n, Both PP and, to a lesser extent, spleen cells from treatment mice p roduced more IgA over a 7-day period than did corresponding control ce lls when cultured without a costimulus or in the presence of either ph orbol myristate acetate plus ionomycin (PMA + ION) or lipopolysacchari de (LPS); IgA elevation was most marked in LPS-treated cultures. The V T 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 secre tion, in LPS-stimulated PP and spleen cell cultures, IL-6 production w as also ablated by M phi depletion, A potential costimulatory role for M phi was further suggested because both IgA and IL-6 production incr eased when M phi-depleted PP cells from VT-treated animals were cocult ured with peritoneal M phi from VT-treated animals, Similar effects we re 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(+) ce lls from VT-treated animals, thus confirming previous studies showing that T cell help also contributes to increased IgA production, Potenti al roles for soluble mediators and cell contact in this process were s uggested when IgA production was measured in cultures of PP cells sepa rated from VT-treated M phi by a semipermeable membrane, Taken togethe r, these and previous results suggest that M phi may play a key mechan istic role in elevated IgA production and IgA nephropathy in VT-expose d mice. (C) 1998 Academic Press.