Immunosuppressive mechanisms in protein-calorie malnutrition
- 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
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MACROPHAGES
BIOLOGICAL FUNCTIONS
PROTEINS
NUTRITIONAL DEFICIENCY
ARACHIDONIC ACID
BIOLOGICAL PATHWAYS
CANDIDA
DIET
IMMUNOSUPPRESSION
IODINE ISOTOPES
MEMBRANE PROTEINS
MICE
NUTRITION
PHOSPHOTRANSFERASES
PROSTAGLANDINS
SUPEROXIDE RADICALS
TRACER TECHNIQUES
ANIMAL CELLS
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CONNECTIVE TISSUE CELLS
ENZYMES
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MICROORGANISMS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHAGOCYTES
PHOSPHORUS-GROUP TRANSFERASES
PLANTS
RADICALS
RODENTS
SOMATIC CELLS
TRANSFERASES
VERTEBRATES
YEASTS
550201* - Biochemistry- Tracer Techniques