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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01270

Targeting endothelium barrier dysfunction caused by circulating bacterial and mitochondrial N-formyl peptides with deformylase

  • 1Department of Surgery, Medical College of Georgia, Augusta University, United States
  • 2Department of Physiology, Medical College of Georgia, Augusta University, United States
  • 3Department of Physiology and Pharmacology, University of Toledo, United States

Despite recent advances in our understanding of the mechanisms underlying systemic inflammatory response syndrome (SIRS) and sepsis, the current therapeutic approach to these critically ill patients is centered around supportive care including fluid resuscitation, vasopressors and source control. The incidence of SIRS and sepsis continues to increase in the United States and patients die due to failure to respond to the traditional therapies of nitric oxide blockade, adrenergic agonists, etc. Bacterial and mitochondrial N-formyl peptides (NFPs) act as damage-associated molecular patterns and activate the innate immune system through formyl peptide receptors (FPR) located in immune and non-immune cells, including the vascular endothelium. The resulting inflammatory response manifests as capillary leak, tissue hypoperfusion and vasoplegia, partially due to endothelium barrier breakdown. Potential strategies to prevent this response include decreasing NFP release, breakdown of NFPs, and blocking NFPs from binding FPR. We propose the use of deformylase, the degrading enzyme for NFPs, as potential therapeutic approach to prevent the deleterious effects of NFPs in SIRS and sepsis.

Keywords: Sepsis, SIRS (for Systemic Inflammatory Response Syndrome), Trauma, DAMPs, Damage-associated molecular patterns, Formyl peptide receptor (FPR) 1, deformylase, Endothelium

Received: 05 Oct 2018; Accepted: 17 May 2019.

Edited by:

Julien Pottecher, Hôpitaux Universitaires de Strasbourg, France

Reviewed by:

Cheng Xue H. Qin, Baker Heart and Diabetes Institute, Australia
Rob Hilgers, College of Pharmacy and Health Sciences, Campbell University, United States  

Copyright: © 2019 Martinez Quinones, Komic, McCarthy, Webb and Wenceslau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Patricia Martinez Quinones, Medical College of Georgia, Augusta University, Department of Surgery, Augusta, United States,