Article

In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation.

Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2010; 107(42):18073-8. DOI: 10.1073/pnas.1008737107
Source: PubMed

ABSTRACT 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.

Full-text

Available from: Baomei Wang, May 05, 2015
0 Followers
 · 
139 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Innate immunity is increasingly recognized as a major player in transplantation. In addition to its role in inflammation in the early post-transplant period, innate immunity shapes the differentiation of cells of adaptive immunity, with a capacity to promote either rejection or tolerance. Emerging data indicate that innate allorecognition, a characteristic previously limited to lymphocytes, is involved in allograft rejection. This review briefly summarizes the physiology of each component of the innate immune system in the context of transplantation and presents the current or promising therapeutic applications, such as cellular, anticomplement and anticytokine therapies.
    Expert Review of Clinical Immunology 02/2015; 11(3):1-13. DOI:10.1586/1744666X.2015.1008453 · 3.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A major goal in regenerative medicine is to identify therapies to facilitate our body׳s innate abilities to repair and regenerate following injury, disease or aging. In the past decade it has become apparent that the innate immune system is able to affect the speed and quality of the regenerative response through mechanisms that are not entirely clear. For this reason there has been a resurgent interest in investigating the role of inflammation during tissue repair and regeneration. Remarkably, there have only been a handful of such studies using organisms with high regenerative capacity. Here we perform a study of the inflammatory response following injury in Xenopus larvae, which are able to achieve scarless wound healing and to regenerate appendages, as a preamble into understanding the role that inflammation plays during tissue repair and regeneration in this organism. We characterized the morphology and migratory behavior of granulocytes and macrophages following sterile and infected wounding regimes, using various transgenic lines that labeled different types of myeloid lineages, including granulocytes and macrophages. Using this approach we found that the inflammatory response following injury and infection in Xenopus larvae is very similar to that seen in humans, suggesting that this model provides an easily tractable and medically relevant system to investigate inflammation following injury and infection in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Developmental Biology 03/2015; 11. DOI:10.1016/j.ydbio.2015.03.008 · 3.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Experimental autoimmune uveoretinitis (EAU) is a widely used experimental animal model of human endogenous posterior uveoretinitis. In the present study, we performed in vivo imaging of the retina in transgenic reporter mice to investigate dynamic changes in exogenous inflammatory cells and endogenous immune cells during the disease process.Methods Transgenic mice (C57Bl/6 J Cx 3 cr1 GFP/+ , C57Bl/6 N CD11c-eYFP, and C57Bl/6 J LysM-eGFP) were used to visualize the dynamic changes of myeloid-derived cells, putative dendritic cells and neutrophils during EAU. Transgenic mice were monitored with multi-modal fundus imaging camera over five time points following disease induction with the retinal auto-antigen, interphotoreceptor retinoid binding protein (IRBP1¿20). Disease severity was quantified with both clinical and histopathological grading.ResultsIn the normal C57Bl/6 J Cx 3 cr1 GFP/+ mouse Cx3cr1-expressing microglia were evenly distributed in the retina. In C57Bl/6 N CD11c-eYFP mice clusters of CD11c-expressing cells were noted in the retina and in C57Bl/6 J LysM-eGFP mice very low numbers of LysM-expressing neutrophils were observed in the fundus. Following immunization with IRBP1¿20, fundus examination revealed accumulations of Cx3cr1-GFP+ myeloid cells, CD11c-eYFP+ cells and LysM-eGFP+ myelomonocytic cells around the optic nerve head and along retinal vessels as early as day 14 post-immunization. CD11c-eYFP+ cells appear to resolve marginally earlier (day 21 post-immunization) than Cx3cr1-GFP+ and LysM-eGFP+ cells. The clinical grading of EAU in transgenic mice correlated closely with histopathological grading.Conclusions These results illustrate that in vivo fundus imaging of transgenic reporter mice allows direct visualization of various exogenously and endogenously derived leukocyte types during EAU progression. This approach acts as a valuable adjunct to other methods of studying the clinical course of EAU.
    Journal of Neuroinflammation 01/2015; 12(1):17. DOI:10.1186/s12974-015-0235-6 · 4.90 Impact Factor