Enhancement of Granulocyte Oxidative Metabolism in Sera from Patients with C2 Deficiency and Systemic Lupus Erythematosus

Abstract

Serum or plasma from 3 patients with C2 deficiency (C2D) and systemic lupus erythematosus (SLE) significantly enhanced chemiluminescence and superoxide anion production by polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate or latex beads. PMN from patients and normal individuals were supranormally activated when resuspended in plasma from these patients. No such effect was seen with plasma from a patient with C2D but with no evidence of SLE, from patients with SLE but not C2D, from patients with C1q or C8 deficiency, from C4-deficient guinea pigs, or NZB-NZW mice. Because oxygen-derived free radicals may cause joint or tissue damage, C2D patients who have or develop this activity in their plasma may be more prone to SLE or other collagen-vascular diseases.

Increased neutrophil oxidative burst metabolism in systemic lupus erythematosus

“…29 The clinical relevance of these findings is underscored by in vivo studies demonstrating that ROS generated by immune complex-stimulated neutrophils contribute to tissue damage. 27,28 This is in agreement with our finding that increased ROS production in neutrophils is intimately related to the occurrence of nephritis in SLE, as previously shown by Moroni et al 29…”

“…29 The clinical relevance of these findings is underscored by in vivo studies demonstrating that ROS generated by immune complex-stimulated neutrophils contribute to tissue damage. 27,28 This is in agreement with our finding that increased ROS production in neutrophils is intimately related to the occurrence of nephritis in SLE, as previously shown by Moroni et al 29 Bacterial cells are potent Toll-like receptor (TLR) stimulators, which are one of the most important pathways of innate immunity activation. S. aureus and other Gram-positive bacteria strongly trigger TLR2, 30,31 while P. aeruginosa stimulates TLR4 and TLR5.…”

“…Different groups have previously shown increased ROS production by SLE neutrophils after several stimuli but not after bacterial stimuli. [22][23][24][25][26][27] In addition SLE serum has been shown to increase the oxidative burst in normal neutrophils from healthy controls in vitro. However, there is some controversy in the literature.…”