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

Jean-Francois Légaré1, Adam Oxner, Olivier Heimrath

  • 1Department of Surgery, Dalhousie University, Halifax, NS, Canada. jean.legare@cdha.nshealth.ca

International Journal of Experimental Pathology
|August 19, 2007
PubMed

Insights

Polymorphonuclear cell (PMN) migration to the heart after ischemia persists for hours, unlike skin inflammation. Both beta2 and alpha4 integrins are crucial for this PMN recruitment.

Area of Science:

  • Immunology
  • Cardiovascular Research
  • Inflammation Biology

Background:

  • Polymorphonuclear cells (PMNs) are implicated in myocardial damage post-ischemia.
  • The precise timing and kinetics of PMN migration to the ischemic myocardium are not well understood.
  • Understanding PMN migration is key to developing targeted therapies for myocardial infarction.

Purpose of the Study:

  • To investigate the kinetics of polymorphonuclear cell (PMN) migration to the myocardium following ischemia.
  • To compare PMN migration patterns in the heart versus dermal inflammatory sites.
  • To determine the role of beta2 and alpha4 integrins in PMN recruitment to the ischemic myocardium.

Main Methods:

  • Isolated, 51Cr-labeled PMNs were injected into Lewis rats at various time points (0, 2, 4, 6 hours) after induced myocardial ischemia.
  • Radioactivity measurements quantified PMN migration to the myocardium and dermal sites.
  • Monoclonal antibody blockade of beta2 and alpha4 integrins assessed their contribution to PMN migration.

Main Results:

  • PMN migration to the ischemic myocardium was sustained between 0-6 hours post-ischemia and significantly higher than in sham controls.
  • In contrast, PMN migration to dermal inflammatory sites peaked early and decreased to background levels by 4-6 hours.
  • Blockade of beta2 integrins reduced PMN migration by 32%, alpha4 integrins by 30%, and combined blockade by 63%.

Conclusions:

  • PMN migration following myocardial ischemia is a prolonged process, distinct from acute dermal inflammation kinetics.
  • Both beta2 and alpha4 integrins play significant, equally important roles in mediating PMN recruitment to the ischemic myocardium.
  • These findings highlight potential therapeutic targets for modulating PMN infiltration in myocardial infarction.

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