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Title: Immunosuppressive mechanisms in protein-calorie malnutrition

Journal Article · · Surgery; (United States)
OSTI ID:5267307
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  1. Univ. of Pennsylvania School of Medicine, Philadelphia (USA)

Protein-calorie malnutrition (PCM) induces immunosuppression leading to increased mortality rates. Impaired macrophage respiratory burst activity (superoxide anion (O2-) generation) occurs in PCM, but cellular mechanisms are unclear. The major pathway resulting in O2- production involves inositol lipid-dependent signal transduction. This study examined the effect of mild versus severe PCM on macrophage O2- generating signal transduction pathways specific for responses to Candida albicans. Mice (CFW/Swiss Webster: n = 300) were randomized to either control or low protein diets for 3 or 8 weeks. Peritoneal macrophages were harvested for O2- production, mannose-fucose receptor (MFR) expression, membrane phospholipid analysis, arachidonic acid (AA) content, prostaglandin E2 (PGE2) production, and protein kinase C levels. O2- release was impaired in both mild and severe PCM. MFR expression was also decreased at these time points. Inositol lipid content was significantly lower at the 8-week time point only, although PGE2 and AA were significantly higher in the low protein diet group at 3 weeks. Protein kinase C levels were unchanged by PCM. Thus, mild PCM significantly increases macrophage-PGE2 production secondary to increased AA phospholipid content, with subsequent inhibition of O2- and MFR expression. Severe PCM inhibits macrophage (O2-) through depletion of critical membrane phospholipid components with subsequent impairment in signal transduction.

OSTI ID:
5267307
Journal Information:
Surgery; (United States), Vol. 110:2; ISSN 0039-6060
Country of Publication:
United States
Language:
English