Immunologically mediated aplastic anemia in mice: evidence of hematopoietic stromal injury and injury to hematopoietic stem cells.
Immunologically mediated aplastic anemia (AA) results when lymph node cells (LNC) from C3H/He mice are injected intravenously (i.v.) into H-2 identical CBA/J mice previously given 600 cGy sublethal total-body gamma irradiation (TBI). Previously, we showed that T lymphocytes injure pluripotent hematopoietic stem cells and cause severe pancytopenia and death in 80 to 100% of mice within 3 to 4 weeks, with changes in the bone marrow suggesting stromal injury. The following models were used to study the stroma: (1) Transplantation of femurs from AA mice into normal syngeneic CBA/J mice. After 6 weeks, colony-forming unit-spleen (CFU-S) levels in the femur implants were measured in both AA and control mice (600 cGy TBI only). (2) Development of Dexter long-term bone marrow cultures from AA and control mice, which were used to support hematopoietic bone marrow cells (colony-forming units-granulocyte/macrophage [CFU-GM]) from normal mice. (3) Cellulose ester membranes (CEM) were coated with hematopoietic stroma from AA and control mice and then implanted intraperitoneally (i.p.) into syngeneic CBA/J mice. Six months later, the CEM were removed and analyzed for the presence of trilineal hematopoiesis and bone. Injury to the hematopoietic stroma was documented by the following: (1) Femurs from AA mice had a decreased number of CFU-S compared to controls; (2) Dexter cultures from AA mice formed abnormal stromal layers with a decreased capacity to support CFU-GM from normal donor mice; and (3) CEM coated with stromal cells from AA mice had a decreased capacity to support trilineal hematopoiesis and bone compared to CEM coated with marrow stroma from control mice.
Knospe
W H
WH
Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Husseini
S G
SG
Chiu
K M
KM
Fried
W
W
D000741:Anemia, Aplastic / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation