A circulating lipopolysaccharide-binding protein (LBP) binds endotoxin and activates macrophages via the CD14 receptor upon the macrophage surface.

A circulating lipopolysaccharide-binding protein (LBP) binds endotoxin and activates macrophages via the CD14 receptor upon the macrophage surface. We have shown that this arrangement is relevant in the lung as LBP significantly contracts the concentration of LPS required to activate human alveolar macrophages, and a specific monoclonal antibody to CD14 block ups the effect of LBP/LPS complexe upon alveolar macrophages. To investigate the potential importance of the LBP/LPS/CD14 hypothesis in the lungs, we measured LP LBP and soluble CD14 in the bronchoalveolar lavage fluid of a prospective series of 125 patients with the adult respiratory distress syndrome (ARDS). Each patient underwent single or more bronchoalveolar lavage (BAL) processs on days 3, 7, or 14 following the attack of ARDS. The adult respiratory distress syndrome occurr following sepsis (n = 35) trauma (n = 41) or other (n = 49) risk factors. For comparison, we also studied normal offers (n = 6) and patients with interstitial lung diseases (n = 12) in whom LP was measured using a chromogenic Limulus assay; and LBP and soluble CD14 were measured according to immunoassay using specific monoclonal antibodies raised to purified human LBP and recombinant human soluble CD14

The LP CD14 and LBP were detectable in the BAL of all of the patients with ARDS in concentrations that were significantly higher than those seen in normal offers The concentrations of LBP and CD14 in ARDS BAL were of similar orders of magnitude, and were approximately 1000-fold higher than the LP concentrations. This LBP:LP ratio substantially increased the macrophage tumor necrosis factor-alpha rejoinder to low concentrations of LP Patients with the highest LP concentrations all had sepsis as the etiology of ARDS, and the highest LP concentrations occurr in patients with sepsis who died. Concentrations of LP in patients with trauma were lower than in patients with sepsis and were not different from those with "other" risk factors for ARDS. flats of LBP and CD14 in BAL were not significantly different in patients with sepsis, trauma, and other risk factors. Thus, LP LBP and soluble CD14 were all detectable in the BAL of patients with ARDS. CD14 and LBP in the airspace may play important parts in modulating the endogenous rejoinders to low concentrations of LP in the lung of patients with ARDS.

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