Characteristics of leucocyte adhesion directly observed in flowing whole blood <i>in vitro</i>

Abbitt, Katherine B.; Nash, Gerard B.

doi:10.1046/j.1365-2141.2001.02544.x

Cited by 36 publications

(48 citation statements)

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“…Some elements of the study reproduce and support previous findings on the shear dependence of adhesion of leukocytes and platelets from flowing blood (3,41,50) and of the tendency for red cell aggregation to increase margination and adhesion of leukocytes (18,32,34). However, by newly analyzing the effects of varying shear rate and stress independently (by manipulating flow rate and suspending phase viscosity), we have been able to show that cell size critically affects the attachment process by influencing velocity and, especially, force experienced by cells at the vessel wall.…”

Section: Discussionsupporting

confidence: 78%

“…Since cell velocity will limit time for formation of bonds and drag will increase the rate of dissociation of formed bonds (10), one can expect that attachment will be possible over a wider range of rates and stresses for platelets than leukocytes, without their needing to evolve even fasteracting receptors. In experimental studies of adhesion from flowing whole blood, leukocyte adhesion to selectins is restricted up to ϳ200 s Ϫ1 (3,27), while platelet adhesion to collagen operates at Ͼ1,000 s Ϫ1 (40,41). Nevertheless, the hypothesis that differences in leukocyte and platelet adhesive function arise from differences in size has not been tested under directly comparable conditions.…”

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confidence: 99%

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Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Watts

Barigou

Nash

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Watts T, Barigou M, Nash GB. Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small? Am J Physiol Heart Circ Physiol 304: H1483-H1494, 2013. First published April 12, 2013 doi:10.1152/ajpheart.00881.2012.-We investigated rheological adaptation of leukocytes and platelets for their adhesive functions in inflammation and hemostasis, respectively. Adhesion and margination of leukocytes or platelets were quantified for blood perfused through capillaries coated with P-selectin or collagen, when flow rate, suspending phase viscosity, red cell aggregation, or rigidity was modified. Independent variation of shear rate and shear stress indicated that the ability of platelets to attach at higher levels than leukocytes was largely attributable to their smaller size, reducing their velocity before attachment, and, especially, drag after attachment. Increasing red cell aggregation increased the number of marginated and adhering leukocytes but inhibited platelet adhesion without effect on the number marginated. Increasing red cell rigidity tended to inhibit leukocyte adhesion but promote platelet adhesion. The effects on platelets may be explained by changes in the depth of the nearwall, red cell-depleted layer; broadening (or narrowing) this layer to greater (or less) than the platelet diameter would decrease (or increase) the normal force applied by red blood cells and make attachment less (or more) efficient. Thus different adhesive capabilities of leukocytes and platelets may arise from their differences in size, both directly because of influence on cell velocity and force experienced at the wall and indirectly through effects of size on margination in the bloodstream and interaction with the cell-free layer. In addition, red cell aggregation (of hitherto uncertain physiological significance) may be useful in promoting leukocyte adhesion in inflamed venules but inhibiting unwanted platelet deposition in veins. blood rheology; leukocyte adhesion; platelet adhesion; margination CIRCULATING LEUKOCYTES and platelets must adhere to the wall of blood vessels to carry out their protective functions in inflammation and hemostasis. Typically, leukocyte adhesion is restricted to postcapillary venules, where the wall shear rate (local velocity gradient) and wall shear stress (frictional drag on the wall) are low (ϳ100 s Ϫ1 and Ͻ1 Pa, respectively) (29, 38). Platelet adhesion is most important in the arterial circulation (with shear rate ϳ1,000 s Ϫ1 and stress Ͼ1 Pa) and, indeed, may be undesirable in slow-flowing veins at risk of thrombosis. Specialized, fast-acting receptors have evolved for the purpose of capture from flow: endothelial cell selectins bind sialylated, fucosylated glycoproteins on leukocytes, and von Willebrand factor (vWF) on collagen matrix binds the glycoprotein Ib complex on platelets (6, 54). The kinetics of these receptor pairs are quite similar (15), suggesting that attachment of the different cells in different regions must depend on their unequal ph...

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Section: Discussionsupporting

confidence: 78%

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confidence: 99%

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Watts

Barigou

Nash

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…A number of studies showed that WBC margination increases significantly as a function of decreasing shear rate (19,42,(45)(46)(47). Similar trends have been reported for particles.…”

Section: Shear Ratesupporting

confidence: 63%

Particle Margination and Its Implications on Intravenous Anticancer Drug Delivery

et al. 2014

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Abstract. "Margination" refers to the movement of particles in flow toward the walls of a channel. The term was first coined in physiology for describing the behavior of white blood cells (WBCs) and platelets in blood flow. The margination of particles is desirable for anticancer drug delivery because it results in the close proximity of drug-carrying particles to the endothelium, where they can easily diffuse into cancerous tumors through the leaky vasculature. Understanding the fundamentals of margination may further lead to the rational design of particles and allow for more specific delivery of anticancer drugs into tumors, thereby increasing patient comfort during cancer treatment. This paper reviews existing theoretical and experimental studies that focus on understanding margination. Margination is a complex phenomenon that depends on the interplay between inertial, hydrodynamic, electrostatic, lift, van der Waals, and Brownian forces. Parameters that have been explored thus far include the particle size, shape, density, stiffness, shear rate, and the concentration and aggregation state of red blood cells (RBCs). Many studies suggested that there exists an optimal particle size for margination to occur, and that nonspherical particles tend to marginate better than spherical particles. There are, however, conflicting views on the effects of particle density, stiffness, shear rate, and RBCs. The limitations of using the adhesion of particles to the channel walls in order to quantify margination propensity are explained, and some outstanding questions for future research are highlighted.

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“…Munn et al (23) showed that the addition of red blood cells to a lymphocyte suspension promoted adhesion of the lymphocytes to endothelial cells even at low hematocrit. Abbitt and Nash (1) showed that the adhesion of isolated neutrophils to P-selectin coatings was negligible when flowing through vertical tubes; however, when flowing in whole blood, many neutrophils were observed to adhere at equivalent volumetric flow rates. In a later work, Abbitt and Nash systematically …”

Section: Discussionmentioning

confidence: 99%

A physical sciences network characterization of circulating tumor cell aggregate transport

King

Phillips

Mitrugno

et al. 2015

American Journal of Physiology-Cell Physiology

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Circulating tumor cells (CTC) have been implicated in the hematogenous spread of cancer. To investigate the fluid phase of cancer from a physical sciences perspective, the multi-institutional Physical Sciences-Oncology Center (PS-OC) Network performed multidisciplinary biophysical studies of single CTC and CTC aggregates from a patient with breast cancer. CTCs, ranging from single cells to aggregates comprised of 2-5 cells, were isolated using the high-definition CTC assay and biophysically profiled using quantitative phase microscopy. Single CTCs and aggregates were then modeled in an in vitro system comprised of multiple breast cancer cell lines and microfluidic devices used to model E-selectin mediated rolling in the vasculature. Using a numerical model coupling elastic collisions between red blood cells and CTCs, the dependence of CTC vascular margination on single CTCs and CTC aggregate morphology and stiffness was interrogated. These results provide a multifaceted characterization of single CTC and CTC aggregate dynamics in the vasculature and illustrate a framework to integrate clinical, biophysical, and mathematical approaches to enhance our understanding of the fluid phase of cancer.circulating tumor cell; metastasis; breast cancer; cell lines; fluid dynamics; physics of cancer; hemodynamics; quantitative phase microscopy; microfluidics; immersed finite element method WHILE THE PRESENCE of circulating tumor cells (CTCs) in the vasculature has been implicated in the metastatic cascade of epithelial carcinomas, new evidence has revealed a putative role of CTC aggregates as a potential form of stromal-assisted metastasis across a variety of epithelial tumor types (6). In concert, the presence of homotypic interactions among CTCs leading to aggregation occurring at sites of endothelial attachment suggest the involvement of CTC aggregates in the hematogenous dissemination of cancer. Despite compelling evidence suggesting a role for CTC aggregates in metastatic progression (28), the physics underlying CTC vascular transport including the influence of blood flow, coagulation, intercellular adhesion, and collisions with cells of the vasculature, such as red blood cells (RBCs) and endothelial cells (ECs), remains poorly understood. Better physical understanding of CTC transport and mechanobiology could enable, for example, new strategies to monitor patient response to chemotherapy (22).Here, we demonstrate a multidisciplinary approach (29) that utilizes clinical measurements on single CTCs and CTC aggregates from a patient with breast cancer as a quantitative guide in the rational design of in vitro and in silico models to investigate the dynamics of CTC transport in the vasculature. Using the high-definition (HD) CTC assay to identify circulating tumor cells in the blood, coupled with quantitative phase microscopy (QPM) to quantify the subcellular density organization of CTCs, we profiled the biophysical properties of CTCs in a patient with breast cancer. These metrics, including geometric and density features,...

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Characteristics of leucocyte adhesion directly observed in flowing whole blood in vitro

Cited by 36 publications

References 37 publications

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Comparative rheology of the adhesion of platelets and leukocytes from flowing blood: why are platelets so small?

Particle Margination and Its Implications on Intravenous Anticancer Drug Delivery

A physical sciences network characterization of circulating tumor cell aggregate transport

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