Kreisel D, Nava RG, Li W et al.In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proc Natl Acad Sci USA 107:18073-18078

Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2010; 107(42):18073-8. DOI: 10.1073/pnas.1008737107
Source: PubMed


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.

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    • "During inflammatory responses, monocytes appear responsible for bringing neutrophils to injured sites in murine models (Kreisel et al., 2010). Neutrophils are essential for microbial clearance by phagocytosis and the release of ROS, superoxides, and a number of proteases (Dhaliwal et al., 2012; Wang et al., 2012; Grainger et al., 2013, Helk et al., 2013). "
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    • "In some models of inflammation, however, CX3CR1+ Ly6Clow monocytes are known to infiltrate inflamed tissue within hours and initiate subsequent immune responses [18]. In addition, CCR2+ monocytes may promote neutrophil extravasation [19], [20]. Reconciling these data requires further attention to the kinetics of monocyte infiltration into inflamed tissue during the earliest steps of the process. "
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    • "Previous reports have described leukocyte recruitment as occurring at capillaries , without the conventional multistep cascade or reliance on either the β2 integrins or selectins (Wang et al. 2004). TP- IVM in a recent study revealed significant numbers of extravascular neutrophils in the lung of mechanically ventilated LysM-green-fluorescent-protein (GFP) transgenic mice at baseline (Kreisel et al. 2010). These neutrophils appear to be weakly motile (~2-3 μm/min). "
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    ABSTRACT: The immune cell system is a critical component of host defense. Recruitment of immune cells to sites of infection, immune reaction, or injury is complex and involves coordinated adhesive interactions between the leukocyte and the endothelial cell monolayer that lines blood vessels. This article reviews basic mechanisms in the recruitment of leukocytes to tissues and then selectively reviews new concepts that are emerging based on advances in live cell imaging microscopy and mouse strains. These emerging concepts are altering the conventional paradigms of inflammatory leukocyte recruitment established in the early 1990s. Indeed, recent publications have identified previously unrecognized contributions from pericytes and interstitial leukocytes and their secreted products that guide leukocytes to their targets. Investigators have also begun to design organs on a chip. Recent reports indicate that this avenue of research holds much promise.
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