Pathogenesis of Multiple Organ Failure: The Impact of Systemic Damage to Plasma Membranes

Frontiers in Medicine

article

Andrey V. Kozlov¹  Johannes Grillari¹ 

[1] Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation With AUVA;Austrian Cluster for Tissue Regeneration, Medical University of Vienna;Laboratory of Navigational Redox Lipidomics and Department of Human Pathology, IM Sechenov Moscow State Medical University;Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences

关键词: multiple organ failure;    plasma membrane;    reactive oxygen species;    phospholipase A2;    pore forming protein;    systemic inflammation and sepsis;    hypoxia;   

DOI  :  10.3389/fmed.2022.806462

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Multiple organ failure (MOF) is the major cause of morbidity and mortality in intensive care patients, but the mechanisms causing this severe syndrome are still poorly understood. Inflammatory response, tissue hypoxia, immune and cellular metabolic dysregulations, and endothelial and microvascular dysfunction are the main features of MOF, but the exact mechanisms leading to MOF are still unclear. Recent progress in the membrane research suggests that cellular plasma membranes play an important role in key functions of diverse organs. Exploration of mechanisms contributing to plasma membrane damage and repair suggest that these processes can be the missing link in the development of MOF. Elevated levels of extracellular phospholipases, reactive oxygen and nitrogen species, pore-forming proteins (PFPs), and dysregulation of osmotic homeostasis occurring upon systemic inflammatory response are the major extracellular inducers of plasma membrane damage, which may simultaneously operate in different organs causing their profound dysfunction. Hypoxia activates similar processes, but they predominantly occur within the cells targeting intracellular membrane compartments and ultimately causing cell death. To combat the plasma membrane damage cells have developed several repair mechanisms, such as exocytosis, shedding, and protein-driven membrane remodeling. Analysis of knowledge on these mechanisms reveals that systemic damage to plasma membranes may be associated with potentially reversible MOF, which can be quickly recovered, if pathological stimuli are eliminated. Alternatively, it can be transformed in a non-resolving phase, if repair mechanisms are not sufficient to deal with a large damage or if the damage is extended to intracellular compartments essential for vital cellular functions.

【 授权许可】

CC BY