TITLE

MICROBIAL MANNAN SUPPRESSES: NEUTROPHIL AND MONOCYE RESPIRATORY BURST AND ENHANCES MYELOPEROXIDASE RELEASE: POSSIBLE MECHANISMS FOR GRANULOMATOUS INFLAMMATORY IN CROHN'S DISEASE

AUTHOR(S)
Mpofu, C.M.; Rhodes, J.M.; Campbell, B.J.; Edwards, S.W.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA58
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Crohn's disease (CD) patients commonly have serum antibodies to baker's yeast (Saccharomyces cerevisiae). The epitope for this antibody is oligomannan, which is present in bacterial and yeast cell walls. CD-like intestinal lesions occur in chronic granulomatous disease, a condition caused by a defect in phagocyte function. We previously reported that oligomannan inhibits the neutrophil respiratory burst in a dose-dependent manner, with a maximal effect at 1 mg/ml. We have now assessed the effect of oligomannan on the respiratory burst in peripheral blood monocytes and have also assessed its effect on myeloperoxidase release from neutrophils. Methods: Neutrophils were purified from heparinised venous blood by a one-step centrifugation method using Neutrophil Isolation Medium. Monocytes were isolated by Ficoll Hypaque separation followed by adherence to plastic wells. The effect of S cerivesiae oligomannan on phorbol ester (PMA) induced-respiratory burst of peripheral blood monocytes was measured by isoluminol-amplified chemiluminescence. Oligomannan dose of 1 mg/ml was used. Granulocyte-macrophage colony stimulating factor (GMCSF) primed neutrophils in the presence/absence of oligomannan were treated with cytochalasin B (CB) and fMLP to stimulate secretion of myeloperoxidase which was then quantified by immunoblotting. Results: Oligomannan (1mg/ml) inhibited peak PMA-stimulated isoluminol-amplified chemiluminescence in peripheral blood monocytes by (mean ± SD) 52.8% ± 6.0. Isoluminol largely measures extracellular superoxide secretion, which is dependent on NADPH oxidase activity. Oligomannan (1mg/ml) increased myeloperoxidase secretion by (mean ± SD) 74% ± 8.4 in fMLP/CB stimulated, primed neutrophils. Secreted myeloperoxidase has been shown to cause local tissue damage that is independent of the phagocyte respiratory burst. Conclusion: S cerivesiae oligomannan causes inhibition of the PMA-induced respiratory burst in...
ACCESSION #
9747678

 

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