{"id":"CONICETDig_86086da77e8060a85b486a1e8ef4e493","dc:title":"Escherichia coli \u03b1-hemolysin induces red blood cell retention in a microfluidic spleen-like device","dc:creator":"Saffioti, Nicolas Andres","dc:date":"2025","dc:description":["\u03b1-hemolysin (HlyA) is a major exotoxin secreted by uropathogenic Escherichia coli (UPEC), known for its ability to lyse red blood cells (RBCs). Although its lytic effects are well characterized, the nonlytic alterations on RBCs, such as increased permeability to Ca2+, osmotic imbalance, and morphological alterations, remain less understood and may be critical in UPEC pathogenesis. This study investigates the impact of these nonlytic alterations on the rheology and mechanics of RBCs using two biomimetic microfluidic devices that model key aspects of RBCs\u2019 circulation. In the first device, which mimics the mechanical deformation of RBCs in narrow capillaries, HlyA sublytic concentrations were found to significantly impair RBC deformability. These changes were accompanied by an increase in cytosolic Ca2+ and volume expansion. In contrast, the nonacylated protoxin ProHlyA neither impaired the deformability of RBCs nor triggered changes in cytosolic Ca2+ or cell volume. The second device, which simulates the RBCs\u2019 filtration by the spleen\u2019s red pulp, revealed that HlyA, but not ProHlyA, increased RBCs\u2019 retention in small gaps resembling splenic fenestrations. The extent of RBCs\u2019 retention was partially mitigated by blocking purinergic signaling, indicating a contribution of the HlyA-induced volume increase in this process. Our results suggest that the increase in cytosolic Ca2+ elicited by HlyA impacts RBCs\u2019 circulation by decreasing RBCs\u2019 deformability and increasing spleen retention. However, this impairment of RBCs\u2019 performance can function as a defense mechanism to aid in the retention of HlyA-bound RBCs, removing them from circulation, and potentially preventing vascular hemolysis."],"dc:format":["application\/zip","application\/vnd.openxmlformats-officedocument.spreadsheetml.sheet","image\/tiff","application\/octet-stream","text\/plain"],"dc:language":["eng"],"dc:type":"dataset","dc:rights":["info:eu-repo\/semantics\/openAccess","https:\/\/creativecommons.org\/licenses\/by-nc-sa\/2.5\/ar\/"],"dc:relation":["info:eu-repo\/grantAgreement\/Ministerio de Ciencia. Tecnolog\u00eda e Innovaci\u00f3n Productiva. Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica\/PICT 2019 03218"],"dc:identifier":"https:\/\/repositoriosdigitales.mincyt.gob.ar\/vufind\/Record\/CONICETDig_86086da77e8060a85b486a1e8ef4e493"}