Interactive dynamics of cell volume and cell death in human erythrocytes exposed to α-hemolysin from Escherichia coli

SAFFIOTTI NICOLAS; LAURI NATALIA; CANE LUCIA; GONZALEZ LEBRERO RODOLFO; ALLEVA KARINA; OSTUNI MARIANO; MOURO-CHANTELOUP ISABELLE; HERLAX VANESA; SCHWARZBAUM PABLO JULIO

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2022

1422-0067

Abstract: α-hemolysin (HlyA) of E. coli binds irreversibly tohuman erythrocytes and induces cell swelling, ultimately leading to hemolysis.We characterized the mechanism involved in water transport induced by HlyA, andanalyzed how swelling and hemolysis might be coupled. Osmotic waterpermeability (Pf) wasassessed by stopped flow light scattering. Preincubation with HlyA strongly reducedPf in control- andAQP1-null RBCs, although the relative Pfdecrease was similar in both cell types. The dynamics of cell volume andhemolysis on RBCs was assessed by electrical impedance, light dispersion andhemoglobin release. Results show that HlyA induced erythrocyte swelling, whichis enhanced by purinergic signaling, and is coupled to osmotic hemolysis. Wepropose a mathematical model of HlyA activity where kinetics of cell volume andhemolysis in human erythrocytes depend on the flux of osmolytes across themembrane, and on the maximum volume that these cells can tolerate. Our resultsprovide new insights to understand signaling and cytotoxicity mediated by HlyAin erythrocytes.