Glutamine depletion potentiates leucocyte-dependent inflammatory events induced by carrageenan or Clostridium difficile toxin A in rats.
This research investigated the effect of glutamine (Gln) depletion on leucocyte-dependent inflammatory events. Rats were treated intraperitoneally, 16 hr prior to the peak of every parameter evaluated, with either 0.9% NaCl, methionine-sulphoximine (MSO, an inhibitor of endogenous Gln synthesis, 25 mg/kg) or with MSO + Gln (MSO as above plus Gln 3 g/kg in three doses). MSO-induced Gln depletion increased paw oedema induced both by carrageenan (Cg) and by Clostridium difficile toxin A (TxA) (66.2% and 45.5%, respectively; P < 0.05). In dextran-injected animals, oedema and myeloperoxidase (MPO) activity were not modified by Gln depletion. In Cg-treated paws, Gln depletion increased MPO activity by 44% (P < 0.05), interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) concentrations by 47% and 52%, respectively (P < 0.05), and immunostaining for TNF-alpha in paw tissue. In TxA-injected paws, Gln depletion increased MPO activity (46%; P < 0.05). Gln depletion increased Cg- and TxA-induced neutrophil migration to subcutaneous air pouches by 56% and 77% (P < 0.05), respectively, but did not affect migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). Gln infusions reversed all the effects of MSO. Leucocyte counts did not differ between groups. Gln depletion potentiates acute inflammation, possibly by increasing neutrophil migration through resident cell activation and production of IL-1beta and TNF-alpha. Gln supplementation reverses these effects and may be useful during inflammatory catabolic stress.
Nascimento
Silvia B
SB
Department of Physiology and Pharmacology, The Federral University of Ceará, Fortaleza, CE, Brazil.
Sousa
Romualdo B
RB
Martins
Marcos Jullian B
MJ
Souza Gomes
Antoniella
A
Souza
Marcellus Henrique L P
MH
Guerrant
Richard L
RL
Cunha
Fernando Q
FQ
Ribeiro
Ronaldo A
RA
Brito
Gerly A C
GA
D000818:Animals; D001427:Bacterial Toxins; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000276:immunology; D004768:Enterotoxins; D005260:Female; D005973:Glutamine / Q000097:blood / Q000172:deficiency / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007958:Leukocyte Count; D008297:Male; D020556:Neutrophil Infiltration / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001427:Bacterial Toxins; D004768:Enterotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C041348:tcdA protein, Clostridium difficile; D005973:Glutamine; D002351:Carrageenan; D009195:Peroxidase