Department of Physiology Zoom Seminar Tomorrow (Friday, June 5) at 11AM

Dr. Yurdagul will present a Zoom seminar entitled “Processing of Apoptotic Cell-Derived Cargo by Macrophages Continues Efferocytosis and Resolves Inflammation” tomorrow, Friday, June 5, 2020, from 11:00-12:00 pm. Zoom call-in particulars are included below. PLEASE NOTE: This is a new, password-protected login.

Dr. Yurdagul received his Ph.D. in Cell Biology and Anatomy from the Louisiana State University Health Science Center (LSUHSC) at Shreveport. He then continued into postdoctoral work in the Department of Medicine at Columbia University. Dr. Yurdagul is presently associate research scientist in the Department of Medicine at Columbia. For the last twelve years, he has been particularly interested in the cellular and molecular mechanisms underlying atherosclerosis. As a graduate student at LSUHSC-Shreveport, he identified a vital role for the vessel microenvironment, including mechanical forces and local deposition of atherogenic factors, in controlling endothelial cell activation. Nearing the end of his graduate work, Dr. Yurdagul became interested in immune cell function, particularly the processes underlying the phagocytic clearance of apoptotic cells (termed “efferocytosis”). He has since explored a novel area of research examining the cellular and molecular mechanisms of how macrophages equip themselves to process the metabolic burden from ingesting apoptotic cells. Understanding the mechanisms behind these processes will generate future directions for treating atherosclerosis and potentially other diseases characterized by chronic, non-resolving inflammation.

Abstract: Phagocytic clearance of apoptotic cells (ACs) by macrophages, termed “efferocytosis,” triggers anti-inflammatory and pro-resolving responses. However, defective efferocytosis drives non-resolving inflammation and plays a particularly prominent role in atherosclerosis, where atherothrombotic cardiovascular disease is the leading cause of death in the industrialized world. For efficient efferocytosis, individual macrophages must internalize multiple ACs over relatively short periods of time, termed “continued efferocytosis.” Because phagolysosomal degradation of an AC delivers a large metabolic load to a macrophage, we used a metabolomics approach to identify what metabolites were elevated after a macrophage phagocytoses an AC. We discovered that the amino acid arginine showed the highest increase over all other amino acids and further demonstrated that macrophages metabolize AC-derived arginine into putrescine through the sequential action of argasine 1 (Arg1) and ornithine decarboxylase (ODC). Silencing either Arg1 or ODC specifically impairs phagocytosis of secondarily-encountered ACs, which can be rescued by exogenous putrescine. Mice lacking myeloid Arg1 showed defective efferocytosis and its pathological consequences both in the thymus after dexamethasone treatment and in atherosclerotic lesions in a mouse model of atherosclerosis regression. Thus, metabolism of AC-derived arginine into putrescine is a critical process that enables macrophages to clear multiple ACs and to avoid the pathological consequences of defective efferocytosis in vivo.

We look forward to seeing everyone tomorrow morning!