Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

Monica Baiula; Roberto Greco; Lucia Ferrazzano; Alberto Caligiana; Klarida Hoxha; Daniele Bandini; Pasquale Longobardi; Santi Spampinato; Alessandra Tolomelli

doi:10.1371/journal.pone.0237746

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

PLoS One. 2020 Aug 18;15(8):e0237746. doi: 10.1371/journal.pone.0237746. eCollection 2020.

Authors

Monica Baiula¹, Roberto Greco², Lucia Ferrazzano², Alberto Caligiana¹, Klarida Hoxha³, Daniele Bandini³, Pasquale Longobardi³, Santi Spampinato¹, Alessandra Tolomelli²

Affiliations

¹ Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
² Department of Chemistry "Giacomo Ciamician", Alma Mater Studiorum -University of Bologna, Bologna, Italy.
³ Hyperbaric Centre, Ravenna, Italy.

Abstract

In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α4 and β2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α4 and β2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α4β1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in β2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α4β1 and β2 was significantly reduced 70 and 67%, respectively), but α4β1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
CD18 Antigens / analysis
CD18 Antigens / metabolism
Cell Adhesion / immunology
Chronic Disease / therapy
Combined Modality Therapy / methods
Female
Follow-Up Studies
Humans
Hyperbaric Oxygenation*
Integrin alpha4beta1 / analysis
Integrin alpha4beta1 / antagonists & inhibitors*
Integrin alpha4beta1 / metabolism
Male
Middle Aged
Neutrophil Infiltration
Neutrophils / immunology*
Neutrophils / metabolism
Peptidomimetics / pharmacology
Peptidomimetics / therapeutic use*
Primary Cell Culture
Skin Ulcer / blood
Skin Ulcer / immunology
Skin Ulcer / pathology
Skin Ulcer / therapy*
Treatment Outcome
Wound Healing / drug effects
Wound Healing / immunology

Substances

CD18 Antigens
Integrin alpha4beta1
Peptidomimetics

Grants and funding

Financial Disclosure: This research study was supported by Fondazione del Monte di Bologna e Ravenna (https://www.fondazionedelmonte.it/) through a grant to AT (FdM/3980; prot. N° 500 bis/2015). The authors were also supported by the University of Bologna (RFO17, RFO18, RFO19) and by Italian Ministry of Education, University and Research with a specific research project (PRIN 2015 project 20157WW5EH) and a grant to the Department of Chemistry “Giacomo Ciamician” of the University of Bologna under the initiative Department of Excellence (L.232 del 01/12/2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.