Infiltration of polymorphonuclear cells into the post-ischaemic myocardium is dependent on beta2 and alpha4 integrins.

Polymorphonuclear cells (PMN) are believed to be important effector cells responsible the myocardial damage seen following ischaemia. However, the exact kinetics of their migration remains controversial. Isolated PMN (10 x 10(6) cells) labelled with (51)Cr were injected into four groups of Lewis rats: 0 h (T0h; n = 13), 2 h (T2h; n = 7), 4 h (T4h; n = 7) or 6 h following ischaemia (T6h; n = 4). In all recipients, a left thoracotomy and ligation of the left anterior descending coronary was performed. Control animals underwent sham thoracotomy (n = 10). All animals were killed at 24 h and the radioactivity in the tissue measured to estimate labelled PMN migration. Monoclonal antibody blockade was also performed in experimental animals to assess the contribution of beta2 and alpha4 integrins to the PMN migration (n = 32). Labelled PMN migration to the myocardium was similar in all experimental groups, T0-T6h (7.2-11 x 10(5) labelled PMN) and significantly higher than sham controls (2.2 x 10(5) labelled PMN; P = 0.03). In contrast PMN migration to dermal inflammatory sites was highest in T0h group, and reached background level in the T4h and T6h groups. beta2 integrin blockade inhibited labelled PMN migration by 32%. Blockade of alpha4 integrin inhibited PMN migration by 30% while the combined beta2 + alpha4 blockade resulted in 63% inhibition of labelled PMN migration compared to treatment with isotype control antibody (P = 0.035). PMN migration following myocardial ischaemia persists over several hours after myocardial infarction and does not follow similar migration kinetics to dermal inflammation. Our findings also suggest that PMN migration is dependent equally on beta2 and alpha4 integrins.