Histamine scavenging attenuates endotoxin-induced acute lung injury.
Histamine is an important mediator of early and late inflammatory responses. Here we asked whether scavenging of endogenous histamine by the arthropod-derived histamine binding protein EV131 diminishes acute respiratory distress syndrome (ARDS) induced by inhaled endotoxin. We demonstrate that EV131 (360 microg given intranasally) reduced endotoxin-induced bronchoconstriction and recruitment of neutrophils. Furthermore, EV131 administration diminished TNF-alpha and protein leak in the bronchoalveolar lavage fluid. The data suggest that histamine attenuates endotoxin-induced bronchoconstriction and neutrophil recruitment. Therefore, scavenging of histamine by EV131 may represent a novel therapeutic strategy in ARDS.
Ryffel
Bernhard
B
CNRS Institute Transgenose, IEM, Orleans, France. bryffel@cnrs-orleans.fr
Couillin
Isabelle
I
Maillet
Isabelle
I
Schnyder
Bruno
B
Paesen
Guido C
GC
Nuttall
Patricia
P
Weston-Davies
Wynne
W
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011968:Receptors, Histamine / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
C518565:EV131 protein, Rhipicephalus appendiculatus; D004731:Endotoxins; D011968:Receptors, Histamine; D009195:Peroxidase