AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |
Back to Blog
Red blood cells misshapen3/24/2023 ![]() ![]() Here we explore the boundaries of these reserves, how they may be breached, and their pathological implications. Aging renders red blood cells more susceptible to PS exposure after osmotic stress ( 5, 6). For example, a decrease in the capacity to maintain phospholipid asymmetry increases the likelihood of recognition by macrophages, that is mediated by the exposure of phosphatidylserine (PS) in the outer leaflet of the red blood cell membrane. Errors that are inborn or flaws that are acquired in the circulation in critical structural, functional, or metabolic red blood cell components are likely to increase the rate at which the weakest links in these defenses are breached. The limits of these reserves, in addition to the resilience provided by the erythropoietic system, may be reached when red blood cells are exposed to pathological processes, such as inflammation ( 4). The absence of conspicuous clinical consequences, such as hemolysis and anemia, of many structural and functional flaws under physiological circumstances indicates that the red blood cell has considerable reserves to maintain structure and function. The role of most of these processes emerges mainly upon recognition of their putative involvement in pathophysiological mechanisms, and in most cases their molecular details become clear only after detailed study in vitro. The gas transport capacity of red blood cells is not only determined by the characteristics of hemoglobin, but also by the capacity to regulate intracellular pH, deformability, ATP production, redox status, resistance to osmotic and mechanical stress, and recognition and removal by the immune system. In addition, there are hardly any data indicating that physiological aging in vivo or in vitro during storage in the blood bank has a notable effect on oxygen supply of the tissues and carbon dioxide removal ( 3). Also, many obvious deviations of the classical discoid red blood cell shape, due to inborn errors in integral membrane proteins and cytoskeletal components, have no obvious clinical implications ( 2). There are many genetically determined, structural abnormalities in the hemoglobin chains that, in most circumstances, do not affect red blood cell integrity and do not seem to affect transport of oxygen binding and release in lungs and tissues, respectively ( 1). The statement that a healthy red blood cell is essential for organismal homeostasis may sound as a truism, but this depends on the functional definition of a healthy red blood cell. Therefore, interventions that reduce the susceptibility of red blood cells to physiological and pathological stress may reduce the extent or progress of neurodegeneration. An exploration of the literature suggests that disturbed red blood cell function may play a role in the pathophysiology of various neurodegenerative diseases. Also, susceptibility may be induced or enhanced by systemic pathological conditions such as inflammation. Through this mechanism, an increased susceptibility of already compromised red blood cells to physiological stress conditions may constitute an additional risk factor in vulnerable individuals. The underlying mutations may not only affect red cell function, but also render neurons in specific brain areas more susceptible to a concomitant reduction in oxygen supply. Our data on the misshapen red blood cells of patients with neuroacanthocytosis illustrate this general mechanism: an abnormal morphology is associated with an increase in the susceptibility of red blood cells to osmotic and mechanical stress, and alters their rheological properties. Often, functional deficits become apparent only when they are subjected to biochemical or mechanical stress in vitro, or to pathological conditions in vivo. The structure of red blood cells is affected by many inborn and acquired factors, but in most cases this does not seem to affect their function or survival in physiological conditions. Department of Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
0 Comments
Read More
Leave a Reply. |