The protective role of secreted CD14

August 01, 2001

The acute-phase response to the presence of LPS or other bacterial metabolites, a key aspect of host defense against infection, can unfortunately be fatal in its own right.

The signaling pathway by which LPS elicits cytokine secretion by monocytes is now fairly well understood, but less is known about the protective mechanisms that limit the hazardous effects of LPS.

The liver filters out the bulk of injected LPS within minutes, and much of the remainder is neutralized by binding to HDL and other circulating lipoproteins. Kitchens et al. now propose an additional level of control, related to interactions between LPS and its receptor, CD14.

A soluble, circulating form of the molecule, sCD14, competes with the monocyte surface-bound form for LPS binding and apparently mediates the transfer of LPS to HDL. Increasing sCD14 should therefore drive LPS from the cell surface to a biologically inactive form. Interestingly, sera from individuals suffering trauma and sepsis accumulate high levels of sCD14.

To test the possibility that this protein moderates the systemic effects of LPS, Kitchens and colleagues immunodepleted sCD14 from sera from people with varying severity of sepsis and studied its effects on LPS binding in cultured monocytes.

Both the exposure of cells to LPS and the consequent secretion of inflammatory cytokines increased when they were cultured with immunodepleted serum. Adding recombinant sCD14 back to control or immunodepleted serum samples had the opposite effect.

The fate of LPS after it binds sCD14 is still uncertain. Because HDL levels decline precipitously during sepsis, the authors suggest that other lipoproteins may serve as a sink for LPS under these conditions.
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JCI Journals

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