DIFFERENTIAL NITRIC-OXIDE AND TNF-ALPHA PRODUCTION OF MURINE KUPFFER CELL SUBFRACTIONS UPON PRIMING WITH IFN-GAMMA AND TNF-ALPHA

Aims/Background: We have previously shown a striking heterogeneity of naive murine Kupffer cells (KC) that depends on cell size. Methods: In the present study, we demonstrate a shift in response of KC fractions separated on cell size by countercurrent elutriation upon priming wit h tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gam ma). Results: Whereas unprimed large KC are most active in the product ion of TNF-alpha and nitric oxide (NO), after priming of KC with TNF-a lpha predominantly small and intermediate sized KC produce TNF-alpha i n response to bacteria. Priming with IFN-gamma enhanced NO production in all KC. A strong synergy, with respect to production of NO, was obs erved when KC subfractions were exposed to a combination of TNF-alpha and IFN-gamma. Concerning TNF-alpha production, priming of KC subfract ions seemed to induce a shift of activity from large KC to smaller KC. Conclusions: The present data demonstrate a clear heterogeneity among murine KC with respect to immunologic response to stimuli. These resu lts demonstrate that KC have different functions in immunologic reacti ons that seem to be related to size.