In vivo optical imaging of cellular inflammatory response in granuloma formation using fluorescence-labeled macrophages.

Full Abstract

Near-infrared imaging such as fluorescence reflectance imaging (FRI) and fluorescence-mediated tomography (FMT) yields high signal-to-noise ratios (SNRs) and should thus be well suited for cell-tracking studies. Extravasation of monocytes or macrophages (Ms) is one of the earliest events in inflammation. The purpose of this study was to assess whether FRI and FMT allow for the visualization and quantification of early inflammatory processes by tracing the migration of fluorescence-labeled murine Ms in a cutaneous granuloma model. METHODS: Ms were labeled with a membrane-selective carbocyanine dye (1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide [DiR]). Cellular viability and function (nitric oxide production, phagocytosis, adherence) were assessed in vitro. Local inflammation was induced in mice by the subcutaneous injection of polyacrylamide gel pellets including or excluding a strong inflammatory stimulus (lipopolysaccharide). Labeled Ms were injected intravenously, and FRI and FMT were performed up to 7 d. SNRs were calculated for the pellets, and the 3-dimensional distribution of Ms was assessed using FMT. Cells were harvested from gel pellets and analyzed by flow cytometry. RESULTS: DiR labeling did not affect cell viability or cell function. FRI revealed the migration of labeled Ms into gel pellets and the homing of Ms to different body compartments. The lipopolysaccharide-containing pellets exhibited significantly higher SNRs than did pellets without lipopolysaccharide. FMT showed that Ms distributed mainly in the periphery of the pellets. The cellular infiltrates extracted from the harvested pellets revealed the presence of approximately 10%-23% DiR-positive Ms-expressing typical markers, confirming the transendothelial migration of injected Ms. CONCLUSION: The tagging of Ms with DiR allows the noninvasive tracking of inflammatory cells for several days in vivo. FRI and FMT are versatile techniques to monitor and quantify cellular inflammatory responses in vivo.

Author information

Author/s: Eisenblätter, Michel (M); Ehrchen, Jan (J); Varga, Georg (G); Sunderkötter, Cord (C); Heindel, Walter (W); Roth, Johannes (J); Bremer, Christoph (C); Wall, Alexander (A);

Affiliation: Department of Clinical Radiology, University Hospital of Muenster, Muenster, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med), published in United States. (Language: eng)

Reference: 2009-Oct; vol 50 (issue 10) : pp 1676-82

Dates: Created 2009/10/01; Completed 2009/11/03;

PMID: 19759121, status: MEDLINE (last retrieval date: 11/3/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.