Antigen presentation in protein-energy malnutrition.
Protein-energy malnutrition is associated with intrinsic defects in macrophage (MO) microbicidal function, but effects on MO-CD4+ cell interaction are unclear. This study examined the effect of protein-energy malnutrition on components of Ag presentation (AP) by peritoneal macrophages (PMO) and splenocyte responses (MLR) in the naive (resident) and infected state (mycobacterium-BCG), and assessed the potential role of prostaglandin (PGE2) and L-arginine-derived nitric oxide (NO) as regulatory mechanisms in these immune interactions. Mice were randomized to receive either a control (24% casein, RD) or low-protein (2.5% casein, LPD) diets for 8 weeks. PMO and splenocytes were harvested and AP function and MLR assessed +/- NG-mono-methyl-L-arginine (NMMA; competitive inhibitor of NO. synthesis) or indomethacin (PGE2 inhibitor). PMO components of AP were evaluated, including phagocytic function, MHC-class II (Ia) expression, and interleukin-1 (IL-1) and interleukin-6 (IL-6) production. PGE2 production and NO. (measured as NO-2) synthesis were also assessed. AP and MLR were preserved in protein-energy malnutrition in both resident and activated states. BCG infection in RD was associated with PMO activation as measured by increased O-2 and NO-2 release, but impaired AP and MLR responses. NMMA and indomethacin enhanced AP and MLR in RD groups only. Individual components of PMO AP (phagocytosis, IL-1 and IL-6 production) were defective during protein-energy malnutrition, as were NO-2 and PGE2 production. Thus, AP and MLR were preserved in LPD groups which may be related to a loss of prostaglandin- and L-arginine-mediated suppressor mechanisms.
Redmond
H P
HP
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Gallagher
H J
HJ
Shou
J
J
Daly
J M
JM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000032:analysis; D011502:Protein-Energy Malnutrition / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000032:analysis; D013154:Spleen / Q000166:cytology
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D015232:Dinoprostone