TY - JOUR
T1 - In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation
AU - Kreisel, Daniel
AU - Nava, Ruben G.
AU - Li, Wenjun
AU - Zinselmeyer, Bernd H.
AU - Wang, Baomei
AU - Lai, Jiaming
AU - Pless, Robert
AU - Gelman, Andrew E.
AU - Krupnick, Alexander S.
AU - Miller, Mark J.
PY - 2010/10/19
Y1 - 2010/10/19
N2 - Immune-mediated pulmonary diseases are a significant public health concern. Analysis of leukocyte behavior in the lung is essential for understanding cellular mechanisms that contribute to normal and diseased states. Here, we used two-photon imaging to study neutrophil extravasation from pulmonary vessels and subsequent interstitial migration. We found that the lungs contained a significant pool of tissue-resident neutrophils in the steady state. In response to inflammation produced by bacterial challenge or transplant-mediated, ischemia-reperfusion injury, neutrophils were rapidly recruited from the circulation and patrolled the interstitium and airspaces of the lung. Motile neutrophils often aggregated in dynamic clusters that formed and dispersed over tens of minutes. These clusters were associated with CD115+ F4/80+ Ly6C+ cells that had recently entered the lung. The depletion of blood monocytes with clodronate liposomes reduced neutrophil clustering in the lung, but acted by inhibiting neutrophil transendothelial migration upstream of interstitial migration. Our results suggest that a subset of monocytes serve as key regulators of neutrophil extravasation in the lung and may be an attractive target for the treatment of inflammatory pulmonary diseases.
AB - Immune-mediated pulmonary diseases are a significant public health concern. Analysis of leukocyte behavior in the lung is essential for understanding cellular mechanisms that contribute to normal and diseased states. Here, we used two-photon imaging to study neutrophil extravasation from pulmonary vessels and subsequent interstitial migration. We found that the lungs contained a significant pool of tissue-resident neutrophils in the steady state. In response to inflammation produced by bacterial challenge or transplant-mediated, ischemia-reperfusion injury, neutrophils were rapidly recruited from the circulation and patrolled the interstitium and airspaces of the lung. Motile neutrophils often aggregated in dynamic clusters that formed and dispersed over tens of minutes. These clusters were associated with CD115+ F4/80+ Ly6C+ cells that had recently entered the lung. The depletion of blood monocytes with clodronate liposomes reduced neutrophil clustering in the lung, but acted by inhibiting neutrophil transendothelial migration upstream of interstitial migration. Our results suggest that a subset of monocytes serve as key regulators of neutrophil extravasation in the lung and may be an attractive target for the treatment of inflammatory pulmonary diseases.
KW - Ischemia
KW - Lung
KW - Transendothelial migration
KW - Transplant
KW - Two-photon microscopy
UR - http://www.scopus.com/inward/record.url?scp=78149258267&partnerID=8YFLogxK
U2 - 10.1073/pnas.1008737107
DO - 10.1073/pnas.1008737107
M3 - Article
C2 - 20923880
AN - SCOPUS:78149258267
SN - 0027-8424
VL - 107
SP - 18073
EP - 18078
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
ER -