Suramin inhibits immune responses and protects cells against inflammatory cell injury. However, little is known about its mechanisms. Using an in vitro model of glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we investigated the potential protective effects and mechanisms of suramin on immunologic cell injury. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused complement-dependent cell lysis, which was blocked by suramin and its structural analogue NF023 and NF049, but not by PPADS, an antagonist of purinergic receptors. Addition of exogenous ATP also failed to affect MC lysis. Further analysis revealed that suramin interfered with antibody binding to cell membrane antigens and suppressed antibody-induced phosphorylation of several proteins, including p38. Inhibition of p38 with chemical inhibitor significantly attenuated cell injury. Collectively, our results indicate that suramin protects cells against antibody-initiated and complement-dependent cell injury through inhibition of antibody binding to cell surface antigens and suppression of p38 activation. Our study thus provides novel mechanistic insights into the actions of suramin and suggests that suramin might be used to treat certain immune diseases.

Antioxidant glutathione (GSH) plays an important role in the regulation of immunity. However, little is known about its effects on humoral immunity, especially its action on effector molecules like antibody and complement. Given that these molecules contain abundant disulfide bonds, we speculated that GSH might influence the action of these proteins via its thiol function. Using a model of a glomerular mesangial cell (MC) lysis induced by antibodies plus complement, we addressed this hypothesis. Exposure of rat MCs to anti-Thy-1 antibody plus complement or anti-MC rabbit serum caused a complement-dependent cell lysis, which was completely blocked by GSH. Moreover, GSH potently prevented the antibody-mediated agglutination of red blood cells and aggregation of antibody-sensitized microspheres. Further analysis revealed that GSH inhibited antibody binding to antigens and promoted the conversion of the antibodies to its reduced forms. GSH also potently inhibited the formation and deposition of C5b-9 in MCs and suppressed both the classic and alternative complement activation pathway. Lastly, GSH attenuated P38 activation, an oxidative sensitive kinase that partially mediated the antibody- and complement-dependent MC lysis. Depletion of GSH via inhibiting gamma-glutamylcysteine synthetase or xCT transporter augmented P38 activation and sensitized MCs to the cell lysis. Collectively, our results indicate that GSH protects cells from immunological cell damage via mechanisms involving inhibition of antibody binding to the antigens, suppression of complement activation and augmentation of cellular defense mechanism. Our study provides novel mechanistic insights into the actions of GSH in the regulation of immune responses and suggests that GSH might be used to treat certain immune disorders.

Background: Backbend-induced pediatric thoracic spinal cord injury without radiologic abnormality (BBPT-SCIWORA) in children is rare in clinical practice and leads to lower limb motor dysfunction. There are few clinical studies on BBPT-SCIWORA and even fewer on treatments for BBPT-SCIWORA-induced lower limb motor dysfunction. Objective: To explore the therapeutic effect of acupuncture at bilateral spine acupoints combined with lower limb acupoints in BBPT-SCIWORA. Case Presentation: This study reported four cases of BBPT-SCIWORA after dancing, two of which received a unique medium-frequency electroacupuncture treatment. They were all females aged between 5 and 12 years old. They were diagnosed with BBPT-SCIWORA by magnetic resonance imaging (MRI), transferred to the rehabilitation department for lower limb dysfunction, and received rehabilitation treatments and acupuncture. Cases 1 and 2 received acupuncture treatment for lower limb acupoints, while Cases 3 and 4 received acupuncture treatment at the bilateral spine acupoints beside the lesion and lower limb acupoints. Cases 3 and 4 achieved better American spinal injury association (AIS) grades and lower extremity motor scores (LEMS) than Cases 1 and 2 after treatment. Conclusion: Acupuncture treatment of beside bilateral spine acupoints plus lower limb acupoints therapy might facilitate early lower limb motor function recovery in children with BBPT-SCIWORA.