In vivo visualization of cardiac allograft rejection and trafficking passenger leukocytes using bioluminescence imaging.

Abstract:

BACKGROUND:We investigated the feasibility of bioluminescence imaging (BLI) for the in vivo assessment of cardiac allograft viability and visualization of passenger leukocytes during the course of acute rejection. METHODS AND RESULTS:Hearts of FVB (H-2q) luciferase-green fluorescent protein transgenic mice (beta-actin promoter) or FVB luciferase transgenic mice (CD5 promoter) were heterotopically transplanted into either BALB/c (H-2d) or FVB recipients. Light intensity emitting from the recipient animals was measured daily by in vivo BLI until 12 days after transplantation. Graft beating score (0 to 4) was assessed by daily abdominal palpation until 12 days after transplantation. Inflammatory cell infiltration (CD45 stain) and structural changes of green fluorescent protein-positive cardiomyocytes were followed by immunohistochemistry. All cardiac allografts were acutely rejected by 12 days after transplantation. The intensity of light emitting from cardiac allografts declined 4 days after transplantation and correlated with graft beating scores (R2=0.91, P=0.02). Immunohistochemistry confirmed these results by showing an increase of CD45+ inflammatory cell infiltration and destruction of green fluorescent protein-positive cardiomyocytes in the cardiac allografts during acute rejection. In vivo BLI visualized migration and proliferation of CD5+ passenger leukocytes in both syngeneic and allogeneic recipients. In the allograft recipients, light signal from CD5+ passenger leukocytes peaked at 6 hours and diminished by 12 hours, whereas in the syngeneic recipients, the signal remained high until 10 days after transplantation. CONCLUSIONS:BLI is a useful modality for the quantitative assessment of in vivo cardiac graft viability and tracking of passenger leukocytes in vivo during the course of acute rejection.

journal_name

Circulation

journal_title

Circulation

authors

Tanaka M,Swijnenburg RJ,Gunawan F,Cao YA,Yang Y,Caffarelli AD,de Bruin JL,Contag CH,Robbins RC

doi

10.1161/CIRCULATIONAHA.104.524777

subject

Has Abstract

pub_date

2005-08-30 00:00:00

pages

I105-10

issue

9 Suppl

eissn

0009-7322

issn

1524-4539

pii

112/9_suppl/I-105

journal_volume

112

pub_type

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