Affiliation:
1. From the Department of Hematology and Istituto di Oncologia and Patologia Sperimentali, Istituto di Anatomia Patologica, University of Florence, and Azienda Ospedaliera Careggi, Florence; Dipartimento di Biomorfologia, Università G. D'Annunzio, Chieti; and Servizio di Qualità and Sicurezza della Sperimentazione Animale, Laboratorio di Biologia Cellulare, and di Biochimica Clinica, Istituto Superiore di Sanità, Rome, Italy.
Abstract
Abstract
The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1low mice) to acute (phenylhydrazine [PHZ]–induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1low mice are profoundly thrombocytopenic (platelet counts [× 109/L] 82.0 ± 28.0 vs 840 ± 170.0 of their control littermates, P < .001) but have a normal hematocrit (Hct) (approximately .47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5+), erythroid (TER-119+), and bipotent (erythroid/megakaryocytic, TER-119+/4A5+) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units–erythroid (BFU-E)– and colony-forming units–erythroid (CFU-E)–derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1low mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P < .01). In response to EPO, the Hct of the GATA-1low mice raised to .68 proportion of 1.0 (68%) vs the .55 proportion of 1.0 (55%) reached by the controls (P < .01). Both the GATA-1low and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1low mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
61 articles.
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