Emollient Eicosonoids

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Science  16 Apr 2004:
Vol. 304, Issue 5669, pp. 363
DOI: 10.1126/science.304.5669.363b

Cystic fibrosis (CF) is an inherited condition that causes progressive lung disease. Although functionally deleterious mutations in the chloride ion transporter CFTR have been identified in CF patients, the sodium and chloride concentrations in their airway surface fluid can be normal, indicating that faulty ion transport is not the whole story.

Karp et al. suggest that anti-inflammatory lipids called lipoxins may link CFTR mutations to CF pathogenesis in the lung. Lipoxins are synthesized by airway epithelial cells and neutrophils in response to infection and are crucial mediators of inflammatory response maturation. Many CF patients suffer from chronic bacterial infections and inflammation. Lipoxins inhibit the acute neutrophil response and also activate macrophages during the second phase of bacterial clearance. In CF patients, however, lipoxin levels in airway fluid are reduced, which may allow excessive neutrophil-mediated damage of the epithelium and subsequent bacterial proliferation. In a mouse model of chronic airway infection, treatment with a lipoxin analog inhibited neutrophil accumulation and decreased bacterial burden in the lungs. As for the link between lipoxin and CFTR, eicosonoid metabolism in epithelial cells may be affected by electrolyte or pH, as decreased expression of lipoxygenases was observed in mice expressing a mutated form of CFTR. — LDC

Nature Immunol. 5, 388 (2004).

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