Abstract The cardiac wound healing response to myocardial infarction (MI) encapsulates inflammatory, proliferative, and maturation phases. Neutrophil degranulation is a major component of the inflammatory phase, inducing both tissue degradation and inflammation amplification. Neutrophil granules released into the infarct region contain a series of enzymes including, but not limited to, matrix metalloproteinases (MMPs), cathepsins, and serine elastase. The main function of these proteases is to breakdown extracellular matrix (ECM) to permit removal of necrotic myocyte debris from the infarct to make way for new ECM scar formation. Excessive protease activity can yield excessive infarct wall thinning. Macrophages and neutrophils communicate throughout the wound healing process, although details on how and why have not been fully elucidated. The goal of this project is to understand how macrophage communication to the neutrophil contributes to MI wound healing. My preliminary studies suggest that murinoglobulin-1 in the macrophage secretome attenuates while galectin-3 exacerbates neutrophil degranulation. The overall net effect to coordinate neutrophil cell physiology is determined, therefore, by the composition of the macrophage secretome. Aim 1 will test the hypothesis that macrophage produced murinoglobulin-1 (MUG-1), an α2-macroglobulin homolog in mice, attenuates neutrophil degranulation to limit infarct wall thinning. Aim 2 will test the hypothesis that macrophage produced galectin-3 promotes neutrophil degranulation to fuel infarct wall thinning. Aim 3 will test the hypothesis that the combination of MUG-1 stimulation with galectin-3 inhibition will synergistically reduce wall thinning and improve cardiac remodeling. Innovation lies in the evaluation of macrophage communication to the neutrophil after MI. We will integrate multi-discipline approaches to explore the mechanisms whereby neutrophils regulate remodeling through effects from the macrophage. This study will drive forward the understanding of the cellular basis of LV remodeling and identify novel intervention targets directed at neutrophils or macrophages.