Macrophages secrete murinoglobulin-1 and galectin-3 to regulate neutrophil degranulation after myocardial infarction.

Autor:	Chalise U; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA., Daseke MJ 2nd; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA.; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Kalusche WJ; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Konfrst SR; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA., Rodriguez-Paar JR; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA., Flynn ER; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA., Cook LM; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Becirovic-Agic M; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA., Lindsey ML; Department of Cellular and Integrative Physiology, Center for Heart and Vascular Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA. merry.lindsey@unmc.edu.; Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE, 68105, USA.
Jazyk:	angličtina
Zdroj:	Molecular omics [Mol Omics] 2022 Mar 28; Vol. 18 (3), pp. 186-195. Date of Electronic Publication: 2022 Mar 28.
DOI:	10.1039/d1mo00519g
Abstrakt:	Inflammation presides early after myocardial infarction (MI) as a key event in cardiac wound healing. Ischemic cardiomyocytes secrete inflammatory cues to stimulate infiltration of leukocytes, predominantly macrophages and neutrophils. Infiltrating neutrophils degranulate to release a series of proteases including matrix metalloproteinase (MMP)-9 to break down extracellular matrix and remove necrotic myocytes to create space for the infarct scar to form. While neutrophil to macrophage communication has been explored, the reverse has been understudied. We used a proteomics approach to catalogue the macrophage secretome at MI day 1. Murinoglobulin-1 (MUG1) was the highest-ranked secreted protein (4.1-fold upregulated at MI day 1 vs. day 0 pre-MI cardiac macrophages, p = 0.004). By transcriptomics evaluation, galectin-3 (Lgals3) was 2.2-fold upregulated ( p = 0.008) in MI day 1 macrophages. We explored the direct roles of MUG1 and Lgals3 on neutrophil degranulation. MUG1 blunted while Lgals3 amplified neutrophil degranulation in response to phorbol 12-myristate 13-acetate or interleukin-1β, as measured by MMP-9 secretion. Lgals3 itself also stimulated MMP-9 secretion. To determine if MUG1 regulated Lgals3, we co-stimulated neutrophils with MUG1 and Lgals3. MUG1 limited degranulation stimulated by Lgals3 by 64% ( p < 0.001). In vivo , MUG1 was elevated in the infarct region at MI days 1 and 3, while Lgals3 increased at MI day 7. The ratio of MUG1 to Lgals3 positively correlated with infarct wall thickness, revealing that MUG1 attenuated infarct wall thinning. In conclusion, macrophages at MI day 1 secrete MUG1 to limit and Lgals3 to accentuate neutrophil degranulation to regulate infarct wall thinning.
Databáze:	MEDLINE
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