Israel Medical Association Journal

Background: Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE[1]-modified β2m[2] has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified β2m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages.

Objectives: To investigate the effect of AGE-modified β2m and AGE-human serum albumin on TNF-α[3] and IL-1β[4] secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.

Methods: Human PMØ[5] were isolated from peritoneal dialysis effluent of stable CAPD[6] patients and were incubated for 24 hours with AGE-modified β2m, β2m, AGE-HSA[7], HSA or lipopolysaccharide. TNF-α or IL-1β secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.

Results: Both AGE-modified β2m and AGE-HSA significantly increased TNF-α and IL-1β secretion by human PMØ in a dose-dependent manner (50–200 μg/ml). In contrast, β2m or HSA had no such stimulatory effect on TNF-α secretion but had a small significant increase in IL-1β secretion.

Conclusions: AGE-modified β2m promotes in vitro TNF-α and IL-1β secretion by human PMØ of CAPD patients. Activation of these macrophages by AGE-modified β2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD. 

Background: Inflammation is a major component in the pathogenesis of asthma. CD14 is an endotoxin (lipopolysaccharide) receptor, and is expressed mainly on monocytes and macrophages. Binding of LPS to CD14 activates the monocyte or macrophage and causes the release of different cytokines.  The soluble form of CD14 is present in serum, and its concentration increases in several clinical conditions, including infections, auto-immune disorders, allergic disorders, and lung diseases.  The possible role of CD14/sCD14 in asthma has been investigated in a few adult patients only.

Objectives: To measure serum concentrations of sCD14 in children with status asthmaticus.

Methods: We compared serum concentration of sCD14 in 10 children with status asthmaticus measured within 24 hours of admission and after recovery from the acute episode.

Results: Levels of sCD14 were significantly higher during acute asthma attacks than at recovery.

Conclusions: The elevated serum levels of sCD14 during status asthmaticus may be the result of the activation of monocytes, macrophages or other cells.  The influence of medications on serum sCD14 cannot be ruled out.  The possible use of sCD14 as a marker of lung inflammation in asthma warrants further investigation. 

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LPS= lipopolysaccharide

SCD14= soluble form of CD14