title: CCR5 and FPR1 mediate neutrophil recruitment in endotoxin-induced lung injury.
abstract: Recruitment of neutrophils, regarded as a key mechanism in acute lung injury (ALI), is orchestrated by cell adhesion molecules and chemokines. While the importance of cell adhesion molecules has been carefully investigated, little is known about the importance of chemokines and their receptors in the recruitment of neutrophils in models of ALI. Wild-type Ccr2(-/-), Ccr5(-/-), Fpr1(-/-) or Fpr2(-/-) mice were exposed to aerosolized lipopolysaccharide and the number of neutrophils in the lung tissue (intravascular, interstitial) and in the bronchoalveolar lavage was quantified. Lack of CCR5 or FPR1, but not CCR2 or FPR2, significantly reduced lung neutrophil infiltration in all compartments. Similarly, blockade of CCR5 or FPR1 with specific antagonists reduced counts of alveolar, interstitial and intravascular neutrophils. Such treatments also inhibited lung edema formation and histological lung tissue alterations, thus underscoring the protective role of CCR5 and FPR1 neutralizing strategies in ALI.
authors.affiliation: European Vascular Center Aachen-Maastricht, RWTH Aachen, Aachen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Grommes
authors.forename: Maik
authors.initials: M
authors.lastname: Drechsler
authors.forename: Oliver
authors.initials: O
authors.lastname: Soehnlein
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D065100:CCR5 Receptor Antagonists; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000473:pathology* / Q000502:physiology; D008297:Male; D000077592:Maraviroc; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000235:genetics*; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D065100:CCR5 Receptor Antagonists; C515335:Ccr2 protein, mouse; D003510:Cyclohexanes; C469988:Fpr1 protein, mouse; D008070:Lipopolysaccharides; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D044042:Receptors, Formyl Peptide; D014230:Triazoles; C481578:formyl peptide receptor 2, mouse; D016572:Cyclosporine; C050025:cyclosporin H; D000077592:Maraviroc