Adhesion of T and B lymphocytes to mouse atherosclerotic aortas: Association with lesion topology and VCAM‐1 expression

Abstract

Objective. Although T and B lymphocytes accumulate in atherosclerotic lesions and play a key role in their growth, the mechanisms involved in the adhesion and recruitment of T and B lymphocytes by the lesions have not been resolved. The aim of this study was to compare T and B lymphocyte adhesion to atherosclerotic arteries and to test the role of VCAM‐1 and ICAM‐1. Material and methods. T and B lymphocytes were labelled with red and green fluorescent dyes and incubated with freshly isolated aortas from apolipoprotein‐E‐deficient mice. In some experiments the aortas were pre‐incubated with specific monoclonal antibodies. After washing, the adhering cells were detected by confocal laser scanning microscopy. Results. The number of T and B lymphocytes that adhered to the aortic intimal surface was similar in both lesioned and non‐lesioned areas and in the shoulder region of the lesions. However, the adhesion of T and B lymphocytes was significantly higher in the shoulder regions compared with the lesioned (p<0.0001) and non‐lesioned areas of the aorta (p<0.0001). After pre‐incubation of the aortas with antibodies against VCAM‐1 or ICAM‐1, the lymphocyte adhesions in lesioned areas were 42 % (p = 0.04) and 55 % (p = 0.17), respectively, of those in lesioned areas that had been pre‐incubated with a control antibody. However, although VCAM‐1 protein expression was most pronounced in the shoulder region, the lymphocyte adhesions in the shoulder region and in non‐lesioned areas were unaffected by pre‐incubation with VCAM‐1 antibodies. Conclusions. The results suggest that adhesion of T and B lymphocytes to mouse aortic endothelium is similar, is affected by lesion topology and is dependent on VCAM‐1 expression over the core of atherosclerotic lesions.

• Adhesion molecules
• atherosclerosis
• lymphocyte adhesion
• T and B cells

Acknowledgements

The study was supported by The Danish Heart Foundation, The Novo Nordisk Foundation and the Danish foundations: Fonden til Lægevidenskabens Fremme and Lægeforeningens Forskningsfond. The hybridoma cell line TIB 120 was kindly provided by Jan P. Christensen, Institute of Medical Microbiology and Immunology, The Panum Institute, University of Copenhagen, Denmark. Finn C. Nielsen gave helpful hints on confocal laser scanning microscopy. Karen Rasmussen and Anne Andersen provided excellent technical assistance. We also thank Jens P. Goetze for carefully reading the manuscript.