β‐Adrenergic agonists regulate cell membrane fluctuations of human erythrocytes

Abstract

Mechanical fluctuations of the cell membrane (CMFs) in human erythrocytes reflect the bending deformability of the membrane‐skeleton complex. These fluctuations were monitored by time‐dependent light scattering from a small area (≈0.25 μm2) of the cell surface by a method based on point dark field microscopy. Exposure of red blood cells (RBCs) to adrenaline (epinephrine) and isoproterenol (isoprenaline) resulted in up to a 45 % increase in the maximal fluctuation amplitude and up to a 35 % increase in the half‐width of the amplitude distribution. The power spectra of membrane fluctuations of control and treated cells revealed that adrenaline stimulated only the low frequency component (0.3‐3 Hz). Analysis of the dose‐response curves of β‐adrenergic agonists yielded an EC50 of 5 × 10−9 and 1 × 10−11 M for adrenaline and isoproterenol, respectively. Propranolol had an inhibitory effect on the stimulatory effect of isoproterenol. These findings show a potency order of propranolol > isoproterenol > adrenaline. The stimulatory effect of adrenaline was a temporal one, reaching its maximal level after 20‐30 min but being abolished after 60 min. However, in the presence of 3‐isobutyl‐1‐methylxanthine, a partial stimulatory effect was maintained even after 60 min. Pentoxifylline and 8‐bromo‐cAMP elevated CMFs. However, exposure of ATP‐depleted erythrocytes to adrenaline or 8‐bromo‐cAMP did not yield any elevation in CMFs. These findings suggest that the β‐agonist effect on CMFs is transduced via a cAMP‐dependent pathway. Deoxygenation decreased CMFs and filterability of erythrocytes by ≈30 %. The stimulatory effect of isoproterenol on CMFs was 2.2‐fold higher in deoxygenated RBCs than in oxygenated cells. Exposure of RBCs to adrenaline resulted in a concentration‐dependent increase in RBC filterability, demonstrating a linear relationship between CMFs and filterability, under the same exposure conditions to adrenaline. These findings suggest that β‐adrenergic agonists may improve passage of erythrocytes through microvasculature, enhancing oxygen delivery to tissues, especially under situations of reduced oxygen tension for periods longer than 20 min.

Erythrocyte plasma membrane–bound ERK1/2 activation promotes ICAM-4–mediated sickle red cell adhesion to endothelium

“…37 CAPs are not only involved in AC association but in actin binding, SH3 binding, and cell morphology maintenance as well. 38,39 Previous observations of increased normal RBC membrane filterability after epinephrine treatment for 20 minutes 40 explain the enhanced phosphorylated CAP1 in normal RBCs after 30 minutes of epinephrine exposure. Furthermore, Shain et al suggested that maintenance of altered cell morphology required persistent increased cAMP levels because of continuous ␤AR stimulation.…”

Protein Kinase A-dependent Phosphorylation of Lutheran/Basal Cell Adhesion Molecule Glycoprotein Regulates Cell Adhesion to Laminin α5

“…Previous studies indicated that the physiologic stress mediator epinephrine acts largely through the ␤2-adrenergic receptor on sickle red blood cells (33)(34)(35)(36)(37). Therefore, we tested whether the ␤2-selective antagonist butoxamine could inhibit epinephrine-stimulated K562-Lu adhesion to laminin.…”

Optical phase nanoscopy in red blood cells using low-coherence spectroscopy

“…RBCs vibrate at rates of 0.3 to 30 Hz. 11 We demonstrated our system capabilities by collecting the spectral data at 20 Hz with an integration time of 1 ms for a period of 30 s. To obtain the change in the cell thickness Δh, the change in the cell OPD is divided by the index of refraction difference between the media and the RBC:…”

“…[8][9][10] The membrane fluctuation amplitude, reflecting the bending and shearing of the membrane, was shown to be directly related to RBC deformability. 11 RBC deformability is vital as it enables the RBC to squeeze through the small body capillaries which are only several micrometers in size. Certain pathological conditions in RBCs, such as spherocytosis, malaria, and sickle cell disease, affect the flexibility of the cells as well as change their dynamic behavior and might hinder the efficacy of oxygen transportation to the tissues.…”