Plasmacytoid dendritic cells control lung inflammation and monocyte recruitment in indirect acute lung injury in mice.
Indirect acute lung injury (ALI, not caused by a direct insult to the lung) represents the first organ dysfunction in trauma patients, with nonpulmonary sepsis being the most common cause of indirect ALI. Dendritic cells (DCs) are thought to participate in a number of inflammatory lung diseases; however, their role in indirect ALI is currently not established. Using a clinically relevant model of indirect ALI induced in mice by hemorrhagic shock followed 24 hours later by polymicrobial septic challenge, we report that mature DC numbers were markedly increased in the lung during indirect ALI. DC depletion induced a significant increase in indirect ALI severity, which was associated with enhanced lung and plasma proinflammatory cytokine concentration and recruitment of proinflammatory CD115(+) monocytes in response to increased lung monocyte chemotactic protein-1 production. Among the different DC subpopulations, plasmacytoid DCs, which were induced and activated in the lung during indirect ALI, were responsible for this effect because their specific depletion reproduced the observations made in DC-depleted mice. As the recruitment of monocytes to the lung plays a central deleterious role in the pathophysiology of indirect ALI, our data therefore position plasmacytoid DCs as important regulators of acute lung inflammation.
Venet
Fabienne
F
Division of Surgical Research, Rhode Island Hospital/Brown University, Providence, RI 02903, USA.
Huang
Xin
X
Chung
Chun-Shiang
CS
Chen
Yaping
Y
Ayala
Alfred
A
D055371:Acute Lung Injury / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D002452:Cell Count; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003713:Dendritic Cells / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D000075983:Nectins; D011014:Pneumonia / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012720:Severity of Illness Index
D015815:Cell Adhesion Molecules; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D000075983:Nectins