Crohn's disease monocytes are primed for accentuated release of toxic oxygen metabolites.
BACKGROUND
Inflammatory bowel disease occurs in regions of the intestine characterized by a bowel content high in bacteria. Intestinal bacteria synthesize cell wall products such as lipopolysaccharide; when normal monocytes or macrophages come in contact with these products, they can be primed to release a number of inflammatory mediators. Mediators such as toxic oxygen metabolites released as part of the respiratory burst may contribute to inflammatory tissue damage. The aim of this study was to determine if monocytes from patients with Crohn's disease are primed by lipopolysaccharide for a greater respiratory burst.


METHODS
The generation of superoxide anion was measured by superoxide dismutase inhibitable reduction of ferricytochrome c.


RESULTS
Freshly isolated monocytes from active untreated Crohn's disease patients (n = 8) showed enhanced stimulated release of superoxide anion when compared with normal monocytes (n = 15; 3.80 +/- 0.12 vs. 1.02 +/- 0.06 nmol/5 min; P < 0.001). We tested the hypothesis that the monocyte priming factor in Crohn's disease serum may be lipopolysaccharide by showing that Crohn's disease serum lost its ability to prime normal monocytes after lipopolysaccharide was removed (0.25 +/- 0.25 nmol/5 min, P < 0.001).


CONCLUSIONS
These studies indicate that bacterial cell wall products may be important proinflammatory molecules involved in the initiation and/or perpetuation of Crohn's disease.
Division of Gastroenterology, Children's Hospital of Philadelphia, Pennsylvania.
R N
RN
Baldassano
S
S
Schreiber
R B
RB
Johnston
R D
RD
Fu
T
T
Muraki
R P
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MacDermott
D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003424:Crohn Disease / Q000209:etiology / Q000276:immunology*; D004731:Endotoxins / Q000097:blood / Q000633:toxicity; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism
D004731:Endotoxins; D013481:Superoxides; D011112:Polymyxin B; D002118:Calcium