Non‐Adsorbing Macromolecules in Plasma Induce Erythrocyte Adhesion to the Endothelium

Abstract

Red blood cell (RBC) adhesion to the endothelium is usually insignificant. However, an enhanced adhesion can be observed in various pathological conditions such as diabetes mellitus or sickle cell disease, which is often accompanied by elevated levels of pro-adhesive plasma proteins such as fibrinogen. In the past, these proteins have only been considered to act as ligands, cross-linking the corresponding receptors on adjacent cells, but the detailed underlying mechanism often remained obscure. This work demonstrates that the presence of non-adsorbing polymers in plasma can also enhance the adhesion efficiency of RBCs to endothelial cells (ECs) through depletion interaction. Furthermore, adhesion of RBCs to ECs may be likewise promoted by the protein fibrinogen through depletion interaction. We propose an alternative mechanism for the pro-adhesive effects of plasma proteins and indicate that depletion interaction might play a significant role for the stabilization and destabilization of blood flow in health and disease.

Macromolecular depletion as a determinant of RBC adhesive interactions: Why blood is thicker than water

“…In fact, industrial applications of depletion flocculation are wide spread, including removing small particles from industrial waste by aggregating these particles, thus allowing mechanical separation from the fluid phase. However, this mechanism has only received minimal recognition in biological systems, even though the existence of depletion layers and the applicability of the depletion model to adhesive interactions of blood cells have been demonstrated in several recent studies [4,5,7,24,25,34,[43][44][45]47].…”

“…1) but soft. Such soft surfaces allow penetration of the depleted molecule and therefore the boundary marking the onset of the polymer concentration does not coincide with the physical surface but depends on the surface structure; the result is different molecular mass dependencies for different molecules and cell types or surfaces [26,28,42,45,47].…”

“…However, several findings that are more recent have shown that depletion interaction plays a major role in RBC-RBC interactions by providing the attractive force causing RBC come into close proximity and form aggregates [4,6,24,25]. Depletion-mediated forces are also a major determinant of RBC-EC adhesion in that they bring cells into close contact, thereby allowing or inducing the formation of stronger specific bonds [25,27,41,[43][44][45].…”

“…In a series of publications, the clear answer has been shown to be "yes". For example, the adhesion of normal RBC is markedly increased in the presence of dextran with a molecular mass greater than 70 kDa [41,45] and specific binding of RBC is significantly enhanced in the presence of non-absorbing macromolecules such as dextran [42][43][44][45]. Interestingly, while 70 kDa dextran promotes RBC aggregation [40] and RBC adhesion to albumin-coated glass [41], it does not induce RBC adhesion to cultured endothelial cells [27], most likely due to differing surface characteristics (e.g., thickness, permeability) between protein adsorbed on glass and endothelial cells grown on a flat surface.…”