Shoichi Nishise,Yuji Takeda,Yuko Nishise,Shoichiro Fujishima,Tomohiko Orii,Sayaka Otake,Takeshi Sato,Yu Sasaki,Hiroaki Takeda,Sumio Kawata

Biological Effect of Anaphylatoxin C5a on the Generation of Anti-inflammatory Substances in Leukocyte Adsorption. Therap. Apher. Dial. 2009 13(6), 509–514. doi:10.1111/j.1744-9987.2009.00779.x 

Anaphylatoxins, which are involved in both pro-inflammatory processes and a variety of anti-inflammatory effects, are produced during granulocyte and monocyte adsorptive apheresis. We noticed the anti-inflammatory effects of C5a, the strongest anaphylatoxin, in granulocyte and monocyte adsorptive apheresis. The aim of this study was to investigate the effect of C5a on interleukin-1 receptor antagonist (IL-1ra) and hepatocyte growth factor (HGF) generation in granulocyte and monocyte adsorption. Peripheral blood containing nafamostat mesilate as an endogenous complement activation inhibitor was divided into four groups: (1) no recombinant C5a added, no contact with cellulose acetate (CA) beads (control group); (2) no C5a added, contact with CA beads; (3) C5a added, no contact with CA beads; and (4) C5a added, contact with CA beads. After incubation, IL-1ra and HGF in plasma were measured. IL-1ra was significantly higher in group 3, in which only C5a was added in the absence of CA beads, compared to groups 2 (P < 0.01) and 4 (P < 0.05). HGF was significantly higher only in group 4, in which C5a was added in the presence of CA beads (P < 0.05), but did not increase in the absence of CA beads. C5a can directly induce IL-1ra generation without the granulocyte and monocyte adsorption stimuli to CA beads, but can synergistically induce HGF generation with the adsorption stimuli, indicating C5a has different effects on IL-1ra and HGF generation.

https://onlinelibrary.wiley.com/doi/10.1111/j.1744-9987.2009.00779.x

Yuji Naito ¹, Tomohisa Takagi, Toshikazu Yoshikawa

J Gastroenterol  2007 Oct;42(10):787-98. doi: 10.1007/s00535-007-2096-y. Epub 2007 Oct 15.

Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity and epithelial injury in inflammatory bowel disease (IBD). Current advances have defined the mechanisms by which neutrophils are activated or migrate across endothelial and mucosal epithelial cells. A better understanding of this process will likely provide new insights into novel treatment strategies for IBD. Especially, activated neutrophils produce reactive oxygen and nitrogen species and myeloperoxidase within intestinal mucosa, which induce oxidative stress. Posttranslational modification of proteins generated by these reactive species serves as a “molecular fingerprint” of protein modification by lipid peroxidation-, nitric oxide-, and myeloperoxidase-derived oxidants. Measurement of these modified proteins may serve both as a quantitative index of oxidative stress and an important new biological marker of clinical relevance to IBD. We have succeeded in the clinical development of a novel granulocyte adsorptive apheresis therapy for IBD. In this review, we discuss current advances in defining the role of neutrophil-dependent oxidative stress in IBD.

https://pubmed.ncbi.nlm.nih.gov/17940831/