Toll-like receptor 2 participates in the response to lung injury in a murine model of pulmonary contusion.
Blunt chest trauma resulting in pulmonary contusion with an accompanying acute inflammatory response is a common but poorly understood injury. We report that Toll-like receptor (TLR) 2 participates in the inflammatory response to lung injury. To show this, we use a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans based on histologic, morphologic, and biochemical criteria of acute lung injury. The inflammatory response to pulmonary contusion in our mouse model is characterized by pulmonary edema, neutrophil transepithelial migration, and increased expression of the innate immunity proinflammatory cytokines IL 1beta and IL 6, the adhesion intracellular adhesion molecule 1, and chemokine (CXC motif) ligand 1. Compared with wild-type animals, contused Tlr2(-/-) mice have significantly reduced pulmonary edema and neutrophilia. These findings are associated with decreased levels of circulating chemokine (CXC motif) ligand 1. In contrast, systemic IL 6 levels remain elevated in the TLR2-deficient phenotype. These results show that TLR2 has a primary role in the neutrophil response to acute lung injury. We suggest that an unidentified noninfectious ligand generated by pulmonary contusion acts via TLR2 to generate inflammatory responses.
Hoth
J Jason
JJ
Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. jhoth@wfubmc.edu
Hudson
William P
WP
Brownlee
Noel A
NA
Yoza
Barbara K
BK
Hiltbold
Elizabeth M
EM
Meredith
J Wayne
JW
McCall
Charles E
CE
D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D003288:Contusions / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005838:Genotype; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000503:physiopathology*; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*
D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1