Neutrophil roles in left ventricular remodeling following myocardial infarction

Abstract

Polymorphonuclear granulocytes (PMNs; neutrophils) serve as key effector cells in the innate immune system and provide the first line of defense against invading microorganisms. In addition to producing inflammatory cytokines and chemokines and undergoing a respiratory burst that stimulates the release of reactive oxygen species, PMNs also degranulate to release components that kill pathogens. Recently, neutrophil extracellular traps have been shown to be an alternative way to trap microorganisms and contain infection. PMN-derived granule components are also involved in multiple non-infectious inflammatory processes, including the response to myocardial infarction (MI). In this review, we will discuss the biological characteristics, recruitment, activation, and removal of PMNs, as well as the roles of PMN-derived granule proteins in inflammation and innate immunity, focusing on the MI setting when applicable. We also discuss future perspectives that will direct research in PMN biology.

Figure 1

Time course of PMN infiltration post-MI. MI was created by permanent ligation of the left anterior descending coronary artery in C57BL/6J mice. Following MI, PMN infiltration peaked at days 1–3, started to decline at day 5, and was present at very low levels from day 7 post-MI. PMNs were stained with anti-mouse neutrophil monoclonal antibody (Cederlane, CL8993AP, 1:100). Representative images from n = 3 stained samples per group. Our own unpublished data.

Figure 2

PMN granules. The types, components, formation order, granule size, and degranulation order of PMN granules. The granule components that have been evaluated in the MI setting are highlighted in green. BPI: Bactericidal/permeability-increasing protein; NGAL: neutrophil gelatinase-associated lipocalin; NRAMP1: natural resistance associated macrophage protein-1; CR1: complement receptor 1.

Figure 3

Mechanisms of action of PMNs on post-MI LV remodeling. Infiltrating PMNs release a wide range of cytokines and chemokines, granule components, and reactive oxygen species, which directly and indirectly regulate immune cell infiltration and function to modulate remodeling response.