Differential nitric oxide and TNF-α production of murine Kupffer cell subfractions upon priming with IFN-γ and TNF-α

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We have previously shown a striking heterogeneity of naive murine Kupffer cells (KC) that depends on cell size.


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-α (TNF-α) or interferon-γ (IFN-γ).


Whereas unprimed large KC are most active in the production of TNF-α and nitric oxide (NO), after priming of KC with TNF-α predominantly small and intermediate sized KC produce TNF-α in response to bacteria. Priming with IFN-γ 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-α and IFN-γ. Concerning TNF-α production, priming of KC subfractions seemed to induce a shift of activity from large KC to smaller KC.


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.

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