Myocardial ischaemia-reperfusion injury in haematopoietic cell-restricted beta1 integrin knockout mice.
Evidence indicates that the intercellular adhesion molecule-1 and its counter-receptor beta2 integrin are cardioprotective proteins during myocardial ischaemia-reperfusion, but no data are available concerning the role of blood cell beta1 integrins in this process. We studied the effects of temporary myocardial ischaemia and reperfusion in blood cell-restricted beta1 integrin knockout mice (beta1(-/-)). The left descending coronary artery in conditional beta1(-/-) integrin (beta1(-/-)), beta1 integrin +/+ (beta1(+/+)) and beta1 integrin -/- bone marrow chimeric (beta1(-/-) 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 beta1(-/-), beta1(+/+) and beta1(-/-) 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 beta1(-/-), beta1(+/+) and beta1(-/-) 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 beta1(+/+) mice, the number of infiltrating neutrophils was significantly reduced in beta1(-/-) and beta1(-/-) 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 beta1 integrin expression in haematopoietic cells results in reduced neutrophil infiltration in the ischaemic regions, but does not influence myocardial damage of ischaemic hearts.
Metzler
Bernhard
B
Department of Cardiology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. bernhard.metzler@uki.at
Haubner
Bernhard
B
Conci
Elisabetta
E
Voelkl
Jakob
J
Jehle
Johannes
J
Bauer
Martina
M
Wolf
Dominik
D
Pachinger
Otmar
O
Xu
Qingbo
Q
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D006413:Hematopoietic System / Q000378:metabolism / Q000473:pathology; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D020107:Troponin T / Q000097:blood
D019012:Integrin beta1; D020107:Troponin T