Interactive Dynamics of Cell Volume and Cell Death in Human Erythrocytes Exposed to α-Hemolysin from Escherichia coli

SAFFIOTI, NICOLAS A.*; LAURI, NATALIA * (* BOTH AUTHORS CONTRIBUTED EQUALLY); CANÉ, LUCIA; GONZALEZ-LEBRERO, RODOLFO; ALLEVA, KARINA; MOURO-CHANTELOUP, ISABELLE; OSTUNI, MARIANO A.; HERLAX, VANESA; SCHWARZBAUM, PABLO JULIO

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2022 vol. 23

1422-0067

α-hemolysin (HlyA) of E. colibinds irreversibly to human erythrocytes and induces cell swelling, ultimatelyleading to hemolysis. We characterized the mechanism involved in watertransport induced by HlyA and analyzed how swelling and hemolysis might becoupled. Osmotic water permeability (Pf)was assessed by stopped-flow light scattering. Preincubation with HlyA stronglyreduced Pf in control- andaquaporin 1-null red blood cells, although the relative Pf decrease was similar in both cell types. The dynamicsof cell volume and hemolysis on RBCs was assessed by electrical impedance,light dispersion and hemoglobin release. Results show that HlyA inducederythrocyte swelling, which is enhanced by purinergic signaling, and is coupledto osmotic hemolysis. We propose a mathematical model of HlyA activity where thekinetics of cell volume and hemolysis in human erythrocytes depend on the fluxof osmolytes across the membrane, and on the maximum volume that these cellscan tolerate. Our results provide new insights for understanding signaling andcytotoxicity mediated by HlyA in erythrocytes.