Nobuhito Kashiwagi , Fumio Saito , Hidetaka Maegawa , Kenta Kaneda, Cytokine 2021 Mar;139:155410.

Objective: Apoptotic cells participate in maintenance of homeostasis of the adaptive immune system. Granulocyte/monocyte adsorptive apheresis (GMA) performed with an Adacolumn has been shown to have clinical efficacy together with immunomodulatory effects for immune-mediated disorder cases, such as inflammatory bowel disease (IBD) or psoriatic arthritis. Although induction of apoptosis in neutrophils by GMA has been observed, the detailed mechanism remains unclear. Methods: To focus on phagocytosis-induced cell death (PICD) that induces apoptotic neutrophils, a comparative study utilizing a GMA-carrier (leukocyte adsorbing carrier for Adacolumn) and yeast particles was performed with in vitro and in vivo examinations. Results: L-selectin was significantly (P = 0.0133) shed, reactive oxygen species (ROS) production was promoted (P = 0.0019), and apoptosis induction was enhanced (P = 0.0087) by peripheral blood co-cultured with the GMA-carrier or yeast particles as compared to incubated blood alone. Furthermore, degranulation of myeloperoxidase, elastase, and lactoferrin was increased by both treatments, while the highest level of interleukin-1 receptor antagonist release was found with GMA-carrier treatment (P = 0.0087) as compared to the yeast particles. Plasma from blood treated with the GMA-carrier showed chemotactic activity, and suppressed neutrophil migration to IL-8 and LTB₄. In vivo results demonstrated that neutrophil chemotaxis to IL-8 was desensitized (P = 0.0078) in rabbits following GMA apheresis, while CXCR1 and CXCR2 expressions in neutrophils were reduced by exposing peripheral blood to the GMA-carrier. Conclusions: GMA may regulate the immune system in patients with an immune-mediated disorder by inducing a biological response of neutrophils with a PICD-like reaction.

https://pubmed.ncbi.nlm.nih.gov/33395614/

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/