Immunosuppressive mechanisms in protein-calorie malnutrition.
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.
Redmond
H P
HP
Department of Surgery University of Pennsylvania School of Medicine, Philadelphia.
Shou
J
J
Kelly
C J
CJ
Schreiber
S
S
Miller
E
E
Leon
P
P
Daly
J M
JM
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008563:Membrane Lipids / Q000032:analysis; D051379:Mice; D011493:Protein Kinase C / Q000032:analysis; D011502:Protein-Energy Malnutrition / Q000276:immunology* / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008563:Membrane Lipids; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D013481:Superoxides; D011493:Protein Kinase C; D015232:Dinoprostone