Increased fetal and extramedullary hematopoiesis in Fas-deficient C57BL/6-lpr/lpr mice.
In this study, we examined the consequences of Fas deficiency on hematopoiesis in C57BL/6-lpr/lpr mice. We found a striking extramedullary increase in hematopoietic progenitor cells, comprising erythroid and nonerythroid lineages alike. These modifications preceded the lymphadenopathy, because early progenitors (colony-forming units-spleen [CFU-S] day 8) were already augmented in day-18 fetal livers of the lpr phenotype. Three weeks after birth, CFU-S increased in peripheral blood and spleen and colony-forming cells (CFU-C) began to accumulate 1 to 3 weeks later. Extramedullary myelopoiesis augmented progressively in Fas-deficient mice, reaching a maximum within 6 months. By then, mature and immature myeloid cells had infiltrated the spleen, the liver, and the peritoneal cavity. Similar changes occurred in C57BL/6-gld/gld mice, indicating that they resulted from Fas/FasL interactions. Medullary hematopoiesis was not significantly modified in adult mice of either strain. Yet, the incidence of CFU-S decreased after Fas cross-linking on normal bone marrow cells in the presence of interferon gamma, consistent with a regulatory function of Fas/FasL interactions in early progenitor cell development. These data provide evidence that Fas deficiency can affect hematopoiesis both during adult and fetal life and that these modifications occur independently from other pathologies associated with the lpr phenotype.
Schneider
E
E
Université René Descartes-Paris V, CNRS UMR 8603, Paris, France. schneider@neckerfr
Moreau
G
G
Arnould
A
A
Vasseur
F
F
Khodabaccus
N
N
Dy
M
M
Ezine
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000196:embryology / Q000503:physiopathology; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D003114:Colony-Forming Units Assay; D053222:Fas Ligand Protein; D005260:Female; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006413:Hematopoietic System / Q000196:embryology*; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000196:embryology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor; D007371:Interferon-gamma