Blood Cell Biomechanics Evaluated by the Single-Cell Micromanipulation

Assessed by the micromanipulation technique, the main mechanical properties of blood cells (red cell and white cell) are reviewed. Hyperelasticity of red blood cell membrane is characterized and corresponding material coefficients are given. Surface tension and cell viscosity of leukocyte are discussed and related values are stated. Some aspects of cell contact mechanics are developed. The fundamentals of mechanics of two elastic cell in contact when adhesion is taken into account is specified

PECAM-1 (CD31) is required for interactions of platelets with endothelial cells after irradiation

Sustained adhesion of platelets to endothelial cells (EC) is believed to contribute to thrombosis and vascular occlusions following radiation exposure leading to organ functional impairment and even death. Our objective was to evaluate the role of platelet endothelial cell adhesion molecule (PECAM)-1 in the prothrombotic response of EC after irradiation. Endothelial PECAM-1 expression was determined by cell-enzyme linked immunosorbent assay (ELISA) on human microvascular EC from lung (HMVEC-L) up to 21 days after a 10 Gy irradiation. Platelet- and leukocyte-endothelial cell interactions were assessed using a flow adhesion assay with fluorescently labeled whole blood, and the function of PECAM-1 in these processes was measured by using blocking antibody. PECAM-1 expression was significantly increased on irradiated HMVEC-L and remained elevated at 21 days. Anti-PECAM-1 antibody significantly inhibited adhesion of single platelets and thrombi on irradiated HMVEC-L. This inhibitory effect persisted at day 21. Anti-PECAM-1 also reduced leukocyte adhesion to irradiated HMVEC-L. The up-regulation of endothelial PECAM-1 following radiation exposure is persistent. PECAM-1 plays a key role platelet adhesion/aggregation on irradiated EC. Therefore, strategies targeting this adhesion molecule may prevent the development of radiation pathologies. © 2004 International Society on Thrombosis and Haemostasis

The Linear Motor in the Human Neutrophil Migration

The kinematics and dynamics of human neutrophils in a narrow glass tube (4.9 $\mu$m to 6.3 $\mu$m in diameter) have been investigated both experimentally and theoretically. Cells were activated by the tri-peptide (fMLP) to migrate through a tube with a mean speed of $0.15\pm 0.03~\mu$m/s (54 activated cells). When a hydrostatic pressure was applied across the cell, the mean speed of the cell leading front linearly decreases when the pressure is increased. At a pressure difference of $1530\pm 140$ Pa (9 activated cells), the cell was forced to stop. The cell migration has been approximated by a tractor-trailer model. The cellular motor (leading front), the tractor, produced a traction force by converting chemical energy into mechanical work. This motor has been characterized as a linear motor with two machine coefficients: (i) the maximum traction $T_0~(37.7$ nN) at $V = 0$, where $V$ is the cellular speed (ii) the maximum cellular speed $V_{\rm max}~(0.15~\mu$m/s). A characteristic time of approximately 100 s was measured for the action cycle of the linear motor. A phenomenological description of the chemotactic machine has been presented

Irradiation Increases the Interactions of Platelets with the Endothelium In Vivo: Analysis by Intravital Microscopy

Adhesion of platelets to the endothelium is believed to be a major factor contributing to thrombosis and vascular occlusion after radiotherapy or endovascular irradiation. In the present study, platelet-endothelium interactions were analyzed in vivo by intravital microscopy in mesenteric venules of mice according to three parameters: (1) platelet rolling, (2) platelet adhesion, and (3) the presence of platelet clusters. A 10-Gy total-body irradiation of mice resulted in an increase in the frequency of appearance of these three types of platelet-endothelium interactions in postcapillary venules 6 and 24 h after exposure, whereas only minor alterations were seen in large venules. In addition, the duration of platelet adhesion was increased 24 h after irradiation in both postcapillary and large venules. However, P-selectin was not up-regulated on the platelet membrane and platelet-leukocytes were not seen rolling together, suggesting that changes in platelet-endothelial cell interaction result from endothelial cell activation rather than platelet activation. Our data suggest that irradiation transforms resting endothelial cells to a pro-adhesive surface for platelets, which could ultimately lead to thrombosis. © 2003 by Radiation Research Society

Pravastatin limits endothelial activation after irradiation and decreases the resulting inflammatory and thrombotic responses

Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis, fibrosis and vascular occlusion after radiation therapy. Statins have been reported to improve endothelial function; however, this beneficial effect on endothelial cells has never been investigated after irradiation. Therefore, using human microvascular endothelial cells from lung that had been irradiated with 5 or 10 Gy, we assessed the effect of pravastatin on endothelial activation by ELISA, cell-ELISA and electrophoretic mobility shift assay and increased blood-endothelial cell interactions by a flow adhesion assay. Pravastatin inhibited the overproduction of monocyte chemoattractant protein 1, IL6 and IL8 and the enhanced expression of intercellular adhesion molecule 1 but had no effect on platelet-endothelial cell adhesion molecule 1 expression. Moreover, pravastatin down-regulated the radiation-induced activation of the transcription factor activator protein 1 but not of nuclear factor-κB. Finally, an inhibition by pravastatin of increased adhesion of leukocytes and platelets to irradiated endothelial cells was observed. The effect of pravastatin was maintained up to 14 days after irradiation and was reversed by mevalonate. Pravastatin exerts persistent anti-inflammatory and anti-thrombotic effects on irradiated endothelial cells. Statins may be considered in therapeutic strategies for the management of patients treated with radiation therapy. © 2005 by Radiation Research Society