{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:32:13Z","timestamp":1788348733388,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,4,15]],"date-time":"2012-04-15T00:00:00Z","timestamp":1334448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p><jats:bold>BACKGROUND:<\/jats:bold> Antibody binding to red blood cells (RBCs) can induce potentially fatal outcomes, including hemolytic transfusion reactions (HTRs), hemolytic disease of the fetus and newborn, and autoimmune hemolytic anemia. The mechanism(s) of RBC destruction following antibody binding is typically thought to require complement activation and\/or the involvement of Fc\u03b3 receptors (Fc\u03b3Rs). In the current report, we analyzed mechanisms of HTRs during incompatible transfusions of murine RBCs expressing human glycophorin\u2003A (hGPA) into mice with anti\u2010hGPA.<\/jats:p><jats:p><jats:bold>STUDY DESIGN AND METHODS:<\/jats:bold> C3 and Fc\u03b3 receptor knockout, splenectomized, Fc\u03b3 receptor blocking antibody\u2013treated, and clodronate\u2010treated mice were passively immunized with anti\u2010hGPA (10F7 or 6A7) and transfused with RBCs expressing the hGPA antigen. Posttransfusion blood and serum were collected and analyzed via flow cytometry and confocal microscopy.<\/jats:p><jats:p><jats:bold>RESULTS:<\/jats:bold> This HTR model results in both rapid clearance and cytokine storm. Neither complement nor Fc\u03b3Rs were required for RBC clearance; in contrast, Fc\u03b3Rs were required for cytokine storm. Circulating aggregates of hGPA RBCs were visible during the HTR. Splenectomy and phagocyte depletion by clodronate had no effect on acute RBC clearance; however, incompatible RBCs reentered over 24 hours in clodronate\u2010treated mice.<\/jats:p><jats:p><jats:bold>CONCLUSION:<\/jats:bold> These data demonstrate a biphasic HTR, the first phase involving sequestration of incompatible hGPA RBCs and the second phase involving phagocytosis of sequestered RBCs. However, the mechanism(s) of phagocytosis in the second phase required neither C3 nor Fc\u03b3Rs. These findings demonstrate novel mechanistic biology of HTRs.<\/jats:p>","DOI":"10.1111\/j.1537-2995.2012.03647.x","type":"journal-article","created":{"date-parts":[[2012,4,16]],"date-time":"2012-04-16T04:33:27Z","timestamp":1334550807000},"page":"2631-2645","source":"Crossref","is-referenced-by-count":43,"title":["Biphasic clearance of incompatible red blood cells through a novel mechanism requiring neither complement nor Fc\u03b3 receptors in a murine model"],"prefix":"10.1111","volume":"52","author":[{"given":"Justine S.","family":"Liepkalns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldad A.","family":"Hod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Stowell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantel 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