Patch-Clamp Untersuchungen an Immunzellen : Beteiligung eines Ionenkanals als generelles Prinzip bei der Zellaktivierung durch mikrobielle Pathogenitätsfaktoren
In human macrophages activation of a MaxiK channel has been shown to be an initial step in the activation of human macrophages by the lipopolisaccharide (LPS) of Gram-negative bacteria. In this work it is shown in patch-clamp experiments that the MaxiK channel is also activated by peptidoglycan (sPG), a cell wall component of Gram-positive bacteria, and the pro-inflammatory cytokine Interleukin-1 (IL-1). Cytokine release from human macrophages induced by each of these stimuli and other bacterial virulence factors is suppressed by the application of the channel blocker paxilline in tissue culture experiments. This implies that MaxiK channel function is essential for the activation of human macrophages. Different possible mechanisms of channel activation by LPS, sPG and IL-1 are discussed. MaxiK activation by phosphorylation as a secondary step after transmembrane signaling via Toll-like (TLR) and IL-1 receptors, respectively, is assumable as a channel activating mechanism by LPS, sPG and IL-1. This implies a functional coupling between the MaxiK channel and other proteins of the signaling machinery, e.g. CD14 and TLRs.
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