title: Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage "Switch" Phenotype.
abstract: Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-β-, TLR/NF-κB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity.
authors.affiliation: Moscow State University of Medicine and Dentistry, Delegatskaya Street 20/1, Moscow 127473, Russia ; Institute of General Pathology and Pathophysiology, Baltijskaya Street 8, Moscow 125315, Russia ; University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Malyshev
authors.affiliation: Moscow State University, GSP-1, Leninskie Gory, Moscow 119991, Russia.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Malyshev
mesh_terms: D000818:Animals; D000066670:Cell Plasticity / Q000502:physiology*; D065150:Cellular Reprogramming / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology