Physiological properties of human erythrocytes in inflammation

Abstract

Abstract. The aim of this mini review was to show data that will could open new biotechnical applications. Physiological properties of the erythrocytes obtained in inflammatory conditions simulated in vitro or in vivo in experimental animal models of inflammation or ex vivo by analysis performed in blood samples from patients with vascular diseases are herein presented. Those data obtained in vivo have been utilized in mathematical models of vascular blood circulation on search biomechanical properties of blood components.Behind the enlargement of scientific knowledge all data could open new questions giving support to create new therapeutic drugs and to ameliorate apparatus for non-invasive detection of vascular circulatory diseases and further surgical interventions.Kewords: Erythrocyte deformability, inflammation, nitric oxide Physiological erythrocytes properties-in vitro studies mimicking inflammatory acute conditionsInflammation or inflammatory response is a natural process of the organism to fight an aggressive internal or external chemical, physical or mechanical stimuli or infection resulting from virus or bacterium presences. Redness, edema, pain and heat are the four cardinal signals of inflammation well known since the antiquity. In case of tissue injury, release of chemical signals like histamine, prostaglandins and nitric oxide (NO) by endothelial cells occurs. NO liberate to vessel lumen is scavenged by erythrocytes through band 3 protein [1]. The NO diffuse also to adjacent smooth muscle cells inducing relaxation [2]. Vasodilation occurs, increases blood flow, augment vessel wall permeability and leukocytes recruitment with transmigration to cell injury site for phagocytes pathogens and cells debris. Vascular endothelial cells changes its phenotypes to participate in the acute inflammation which involve a fast and a slower responses in close relation with the blood cells [3]. Acute phase proteins like fibrinogen, oxLDL as well as the non-cholinergic molecule acetylcholine (ACh) levels increase in plasma [4][5][6]. It was showed that the erythrocyte when in presence of ACh, the natural of substrate of the membrane acetylcholinesterase (AChE) release NO which efflux is quantified by amperometric measurement with amiNO-sensor [7,8]. It was verified that the AChE-ACh enzyme active complex activate the protein kinase C (PKC) which in turn phosphorylate the protein tyrosine kinase (PTK) turning it from inactive to active state. PTK phosphorylate band 3 protein became able to receive NO in its thiol group from S-nitrosohemoglobin for delivery to extracellular medium [9][10][11][12]. PKC inhibited by phosphorylation protein tyrosine phosphatase (PTP) and also the phosphodiesterase 3 (PDE3) which consequently do not hydrolyzes the cyclic adenosine triphosphate (cAMP) [9,10]. The AChE-ACh

Human Erythrocyte Acetylcholinesterase in Health and Disease

“…When the inhibitor of the erythrocyte Casein Kinase 2 (a cytosol protein that phosphorylates band 3 protein) is present in the erythrocytes suspensions at high fibrinogen concentration, the NO efflux is maintained as normal, confirming the dependence on band 3 phosphorylation [ 75 , 76 ].…”

Erythrocyte Nitric Oxide

“…When phosphorylation of the erythrocyte membrane protein band 3 is induced in the presence of high fibrinogen concentration and in the absence or presence of 4N1K, the NO efflux increases [46,47]. The NO efflux from erythrocytes at high fibrinogen concentration is dependent on band 3 protein phosphorylation which was confirmed in the experiments where the erythrocyte casein kinase 2 (a cytosol protein that phosphorylates the band 3 protein) inhibitor was used, showing unchanged levels of NO efflux in relation to its absence [27,48].…”

“…Besides, a higher NO efflux from RBC will be expected resulting of the presence of ACh and high fibrinogen concentration, normal values were obtained; the AChE-ACh molecular conformational state activates PKC which inhibits PDE 3 with increase of cAMP concentration that normalize the lower levels of cAMP derived from the inhibition of AC [35,38,45,49]. Interestingly, the presence of forskolin (activator of the enzyme AC) in an in vitro model of hyperfibrinogenemia did not change the levels of NO efflux from erythrocytes, because the PDE3 is functional to hydrolase cAMP [27,48].…”

“…Hemorheology is the science which studies blood deformation and its components' interaction with vessel walls, occurring inside blood vessels of macro and microcirculation. In the past, the longitudinal and follow-up clinical studies done, ex vivo, have as an objective the characterization of the intravascular profile of different diseases according to hemorheological parameters and inflammatory factors [41,48,59]. To accomplish this aim, blood samples were taken from patients with acute myocardial infarction, glaucoma, Bechet, renal diseases whether submitted or not to chronic hemodialysis or kidney transplant and diabetic retinopathy degree, and an association between the laboratorial data and the clinical parameter values was observed [41,48,59].…”

Erythrocyte Acetylcholinesterase is a Signaling Receptors

“…The acute phase protein fibrinogen binds to RBCs membrane CD47protein partner of the Rh macro-complex which is connected to the cytoskeleton via protein 4.2, and interacts also with the major RBC macro--complex band 3 protein [37]. The presence of AChE-ACh and AChE-timolol complexes in RBCs induced the return to normal values the higher NO efflux obtained under high fibrinogen concentration [35,[38][39][40]. Consequently this NO scavenged avoids the increase concentrations of the reactive nitrogen and oxygen species present in inflammatory conditions.…”