title: Mitochondrial N-formyl peptides cause airway contraction and lung neutrophil infiltration via formyl peptide receptor activation.
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.
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA. Electronic address: camillawenceslau@hotmail.com.
authors.forename: Camilla Ferreira
authors.initials: CF
authors.lastname: Wenceslau
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: Theodora
authors.initials: T
authors.lastname: Szasz
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: Cameron G
authors.initials: CG
authors.lastname: McCarthy
authors.affiliation: Department of Oral Biology, Augusta University, Augusta, GA, USA.
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.affiliation: Department of Physiological & Technological Nursing, Augusta University, Augusta, GA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: NeSmith
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D006801:Humans; D055370:Lung Injury / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D012131:Respiratory Insufficiency / Q000503:physiopathology; D018805:Sepsis / Q000503:physiopathology; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology; D055815:Young Adult
chemical_list: D044042:Receptors, Formyl Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine
keywords: Airway and lung inflammation; Mitochondrial N-formyl peptides; Trauma