Formation of erythrocyte rouleaux in preheated normal serum: roles of albumin polymers and lysophosphatidylcholine.

The role of humoral factors in cell-cell interactions was studied in a simple model system: the aggregation of erythrocytes into cylindrical rouleaux when suspended in normal serum preheated at 62 degree C for 20 min. The rouleaugenic activity of heated serum was associated with an increased concentration of albumin polymers. On heating above 62 degree C, albumin released ligands, such as lysophosphatidylcholine, in quantities sufficient to convert erythrocytes to acanthocytes. The latter did not participate in rouleaux formation. Thus normal serum only became rouleaugenic when heated over a narrow range of temperatures. These properties of serum were reproduced in a system consisting only of erythrocytes, heated albumin, and lysophosphatidylcholine. Rouleau formation increased as albumin polymer size increased. Unheated normal serum could also be made rouleaugenic merely by concentrating to above normal physiological concentrations. Unheated, unconcentrated, sera from patients with various diseases are known to be rouleaugenic, but polymeric albumin appears infrequently in such sera; usually there are increases in macroglobulins are large polymeric forms of smaller serum proteins. Current evidence is consistent with the hypothesis that a small shift in the concentration of one or more of these macromolecules above a critical value promotes a phase separation of erythrocytes which spontaneously aggregate to form rouleaux.