Targeting endothelial barrier dysfunction caused by circulating bacterial and mitochondrial n-formyl peptides with deformylase

Patricia Martinez-Quinones, Amel Komic, Cameron G. McCarthy, R Clinton Webb, Camilla Ferreira Wenceslau

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number1270
JournalFrontiers in immunology
Volume10
Issue numberJUN
DOIs
StatePublished - Jan 1 2019

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peptide deformylase
Systemic Inflammatory Response Syndrome
Peptides
Formyl Peptide Receptor
Sepsis
Vasoplegia
Adrenergic Agonists
Vascular Endothelium
Critical Illness
Resuscitation
Endothelium
Immune System
Nitric Oxide
Therapeutics

Keywords

  • DAMPs
  • Deformylase
  • Endothelium
  • Formyl peptide receptor-1
  • SIRS
  • Sepsis
  • Trauma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Targeting endothelial barrier dysfunction caused by circulating bacterial and mitochondrial n-formyl peptides with deformylase. / Martinez-Quinones, Patricia; Komic, Amel; McCarthy, Cameron G.; Webb, R Clinton; Wenceslau, Camilla Ferreira.

In: Frontiers in immunology, Vol. 10, No. JUN, 1270, 01.01.2019.

Research output: Contribution to journalArticle

Martinez-Quinones, Patricia ; Komic, Amel ; McCarthy, Cameron G. ; Webb, R Clinton ; Wenceslau, Camilla Ferreira. / Targeting endothelial barrier dysfunction caused by circulating bacterial and mitochondrial n-formyl peptides with deformylase. In: Frontiers in immunology. 2019 ; Vol. 10, No. JUN.
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