Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation

Camilla Ferreira Wenceslau, Theodora Szasz, Cameron G. McCarthy, Babak Baban, Elizabeth G. NeSmith, R Clinton Webb

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Respiratory failure is a common characteristic of systemic inflammatory response syndrome (SIRS) and sepsis. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns (DAMPs). Mitochondrial N-formyl peptides (F-MITs) are DAMPs that share similarities with bacterial N-formylated peptides, and are potent immune system activators. Recently, we observed that hemorrhagic shock-induced increases in plasma levels of F-MITs associated with lung damage, and that antagonism of formyl peptide receptors (FPR) ameliorated hemorrhagic shock-induced lung injury in rats. Corroborating these data, in the present study, it was observed that F-MITs expression is higher in plasma samples from trauma patients with SIRS or sepsis when compared to control trauma group. Therefore, to better understand the role of F-MITs in the regulation of lung and airway function, we studied the hypothesis that F-MITs lead to airway contraction and lung inflammation. We observed that F-MITs induced concentration-dependent contraction in trachea, bronchi and bronchioles. However, pre-treatment with mast cells degranulator or FPR antagonist decreased this response. Finally, intratracheal challenge with F-MITs increased neutrophil elastase expression in lung and inducible nitric oxide synthase and cell division control protein 42 expression in all airway segments. These data suggest that F-MITs could be a putative target to treat respiratory failure in trauma patients.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalPulmonary Pharmacology and Therapeutics
Volume37
DOIs
StatePublished - Apr 1 2016

Fingerprint

Formyl Peptide Receptor
Neutrophil Infiltration
Infiltration
Chemical activation
Systemic Inflammatory Response Syndrome
Lung
Peptides
Hemorrhagic Shock
Wounds and Injuries
Respiratory Insufficiency
N-Formylmethionine Leucyl-Phenylalanine
Plasmas
Sepsis
Leukocyte Elastase
Immune system
Nitric Oxide Synthase Type II
Bronchioles
Rats
Adult Respiratory Distress Syndrome
Lung Injury

Keywords

  • Airway and lung inflammation
  • Mitochondrial N-formyl peptides
  • Trauma

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation. / Wenceslau, Camilla Ferreira; Szasz, Theodora; McCarthy, Cameron G.; Baban, Babak; NeSmith, Elizabeth G.; Webb, R Clinton.

In: Pulmonary Pharmacology and Therapeutics, Vol. 37, 01.04.2016, p. 49-56.

Research output: Contribution to journalArticle

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