Granulocyte and monocyte adsorptive apheresis induces apoptosis of neutrophils and release of a novel chemoattractant for desensitization of interleukin-8 response - In vitro and in vivo results

Cytokine. 2021 Mar;139:155410. doi: 10.1016/j.cyto.2020.155410. Epub 2021 Jan 1.

Abstract

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.

Keywords: Adaptive immune system; Apoptosis; Granulocyte/monocyte adsorptive apheresis; Inflammatory bowel disease; Phagocytosis-induced cell death; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Adsorption / immunology
  • Animals
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • Arthritis, Psoriatic / immunology
  • Arthritis, Psoriatic / metabolism
  • Blood Component Removal / methods
  • Chemotactic Factors / immunology
  • Chemotactic Factors / metabolism*
  • Granulocytes / immunology
  • Granulocytes / metabolism*
  • Humans
  • Immune System Diseases / immunology
  • Immune System Diseases / metabolism
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism*
  • Male
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Rabbits
  • Treatment Outcome

Substances

  • Chemotactic Factors
  • Interleukin-8