Myocardial ischaemia-reperfusion injury in haematopoietic cell-restricted beta 1 integrin knockout mice

Evidence indicates that the intercellular adhesion molecule-1 and its counter-receptor β2 integrin are cardioprotective proteins during myocardial ischaemia–reperfusion, but no data are available concerning the role of blood cell β1 integrins in this process. We studied the effects of temporary myocardial ischaemia and reperfusion in blood cell-restricted β1 integrin knockout mice (β1−/−). The left descending coronary artery in conditional β1−/− integrin (β1−/−), β1 integrin +/+ (β1+/+) and β1 integrin −/− bone marrow chimeric (β1−/− BM) mice was ligated for 30 min, followed by reperfusion of either 3 h or 3 weeks. Plasma levels of troponin T were evaluated as an index of cardiac cellular damage. The histological evaluation of tissue damage was performed with Haematoxylin and Eosin stained sections. Cell infiltrations in the ischaemic area were investigated by immunofluorescence studies. It was found that plasma troponin T was at a similar level in β1−/−, β1+/+ and β1−/− BM mice treated with 30 min ischaemia and 3 h reperfusion. Histological analysis showed that ischaemia–reperfusion resulted in marked myocardial injury in all groups of animals, but the damage score of the hearts was not significantly different between β1−/−, β1+/+ and β1−/− BM mice after 3 h of reperfusion following 30 min of ischaemia (2.8 ± 0.5, 2.6 ± 0.5 and 2.8 ± 0.6, respectively, n.s.). Furthermore, no difference in scar sizes in ischaemia-injured hearts was found 3 weeks after ischaemia. Semi-quantification of cells demonstrated that, compared with β1+/+ mice, the number of infiltrating neutrophils was significantly reduced in β1−/− and β1−/− BM mice, whereas MAC-1(CD11b/CD18)-positive cells in the ischaemic regions were similar in myocardial tissues of all groups. We conclude that absence of β1 integrin expression in haematopoietic cells results in reduced neutrophil infiltration in the ischaemic regions, but does not influence myocardial damage of ischaemic hearts.