Mitochondrial-derived N-formyl peptides: Novel links between trauma, vascular collapse and sepsis

C. F. Wenceslau, C. G. McCarthy, S. Goulopoulou, T. Szasz, Elizabeth G. NeSmith, R Clinton Webb

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Sepsis is a major cause of mortality and morbidity in trauma patients despite aggressive treatment. Traumatic injury may trigger infective or non-infective systemic inflammatory response syndrome (SIRS) and sepsis. Sepsis and SIRS are accompanied by an inability to regulate the inflammatory response but the cause of this perturbation is still unknown. The major pathophysiological characteristic of sepsis is the vascular collapse (i.e., loss of control of vascular tone); however, at the cellular level the final mediator of extreme vasodilatation has yet to be identified. After trauma, cellular injury releases endogenous damage-associated molecular patterns (DAMPs) that activate the innate immune system. Mitochondrial DAMPs express at least two molecular signatures, N-formyl peptides and mitochondrial DNA that act on formyl peptide receptors (FPRs) and Toll-like receptor 9, respectively. N-Formyl peptides are potent immunocyte activators and, once released in the circulation, they induce modulation of vascular tone by cellular mechanisms that are not completely understood. We have observed that N-formyl peptides from bacterial (FMLP) and mitochondrial (FMIT) sources induce FPR-mediated vasodilatation in resistance arteries. Accordingly, we propose that tissue and cellular trauma induces the release of N-formyl peptides from mitochondria triggering inflammation and vascular collapse via activation of FPR and contributing to the development of sepsis. The proposed hypothesis provides clinically significant information linking trauma, mitochondrial N-formyl peptides and inflammation to vascular collapse and sepsis. If our hypothesis is true, it may lead to new strategies in the management of sepsis that can help clinicians effectively manage non-infectious and infectious inflammatory responses.

Original languageEnglish (US)
Pages (from-to)532-535
Number of pages4
JournalMedical Hypotheses
Volume81
Issue number4
DOIs
StatePublished - Oct 1 2013

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Blood Vessels
Sepsis
Peptides
Formyl Peptide Receptor
Wounds and Injuries
Systemic Inflammatory Response Syndrome
Vasodilation
Toll-Like Receptor 9
Inflammation
Mitochondrial DNA
Immune System
Mitochondria
Arteries
Morbidity
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mitochondrial-derived N-formyl peptides : Novel links between trauma, vascular collapse and sepsis. / Wenceslau, C. F.; McCarthy, C. G.; Goulopoulou, S.; Szasz, T.; NeSmith, Elizabeth G.; Webb, R Clinton.

In: Medical Hypotheses, Vol. 81, No. 4, 01.10.2013, p. 532-535.

Research output: Contribution to journalArticle

Wenceslau, C. F. ; McCarthy, C. G. ; Goulopoulou, S. ; Szasz, T. ; NeSmith, Elizabeth G. ; Webb, R Clinton. / Mitochondrial-derived N-formyl peptides : Novel links between trauma, vascular collapse and sepsis. In: Medical Hypotheses. 2013 ; Vol. 81, No. 4. pp. 532-535.
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