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 with tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma).
Results: Whereas unprimed large KC are most active in the production of TNF-alpha and nitric oxide (NO), after priming of KC with TNF-alpha predominantly small and intermediate sized KC produce TNF-alpha in response to bacteria. Priming with IFN-gamma enhanced NO production in all KC. A strong synergy, with respect to production of NO, was observed when KC subfractions were exposed to a combination of TNF-alpha and IFN-gamma. Concerning TNF-alpha production, priming of KC subfractions 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 results demonstrate that KC have different functions in immunologic reactions that seem to be related to size.