Oxygen radical production and severity of the Guillain--Barré syndrome.
The NADPH oxidase-dependent formation of reactive oxygen species ("oxygen radicals") by phagocytic cells constitutes an important part of the innate immune defence against microorganisms. Recent studies in animal models imply that a deficient function of the NADPH oxidase may be linked to the development of autoimmunity, but a link between oxygen radical production and severity of autoimmune disease in humans has not been established. We have examined the oxygen radical production in peripheral blood leukocytes from patients with the Guillain-Barré syndrome (GBS). Leukocytes from GBS patients in a stationary phase 1-5 years after their acute episode were activated by the formyl peptide receptor (FPR) ligand formyl-Met-Leu-Phe (fMLF) or the closely related formyl peptide like receptor 1 (FPRL1) ligand Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM). The patients were dichotomized according to severity by 1) the requirement of intensive care unit treatment and 2) the ability to walk independently after 3 months. Our data show that the amount of superoxide release following challenge with either of the two agonists fMLF and WKYMVM was significantly lower in patients requiring intensive care unit treatment or unable to walk after 3 months. Results obtained with the global activator phorbol myristate acetate, as well as with fMLF in TNF alpha-primed leukocytes, suggested that the deficiency of oxygen radical production in patients with severe GBS was the result of a specific deficiency of radical production in response to FPR/FPRL1 ligands rather than an inherent deficiency of NADPH oxidase function.
Mossberg
Natalia
N
Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Göteborg, Sweden.
Andersen
Oluf
O
Nilsson
Staffan
S
Dahlgren
Claes
C
Hellstrand
Kristoffer
K
Lindh
Magnus
M
Svedhem
Ake
A
Bergström
Tomas
T
Movitz
Charlotta
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020275:Guillain-Barre Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012720:Severity of Illness Index; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D009842:Oligopeptides; D017382:Reactive Oxygen Species; C113617:Trp-Lys-Tyr-Met-Val-Met; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; C023976:N-formylmethionyl-methionyl-phenylalanine; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate