Defective monocyte-to-macrophage maturation in patients with aplastic anemia.
Macrophages (MAC) are important effector cells of the immune system but also play an essential role as regulatory cells in hematopoiesis. They originate from circulating monocytes (MO) as immature precursor cells that undergo terminal differentiation upon migration from the capillary bed into the various tissues. In the presence of serum, MAC maturation from blood MO is observed in vitro and can be followed by the expression of maturation-associated antigens (MAX.1, .3, .11, and .26; transferrin receptor, 13C2, CD16). We have tested blood MO from 22 patients with aplastic anemia (AA) for their capacity to undergo terminal maturation in vitro. After isolation, blood MO in six patients expressed CD14 molecules at low density when compared to normals. On culture for 7 days, in 15 patients various abnormalities could be shown by phenotype analysis using cell-enzyme-linked immunosorbent assay (ELISA) and an immunoperoxidase staining technique of single cells. Abnormalities ranged from the distinctive failure of mature MAC to express single surface antigens (eg, gp64-MAX.1) to complete inhibition of the development of a MAC maturation-associated phenotype. In three patients the maturational defect was found to persist in complete remission after successful therapy with antileukocyte globulin (ALG). Neither in other immunosuppressed or multiple-transfused patients nor in those with bone marrow hypoplasia secondary to cancer chemotherapy and during hematologic reconstitution following autologous bone marrow transplantation (BMT), defective MO maturation in vitro was seen. Our data provide evidence for the existence of serious disorders within the MO-MAC lineage in patients with AA. This observation may either reflect the stem-cell defect or indicate a MAC involvement in the pathogenesis of the disease.
Andreesen
R
R
Department for Hematology and Oncology, Albrecht-Ludwigs-Universität Freiburg i. Brsg., FRG.
Brugger
W
W
Thomssen
C
C
Rehm
A
A
Speck
B
B
Löhr
G W
GW
D000741:Anemia, Aplastic / Q000473:pathology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006410:Hematopoiesis; D006801:Humans; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D009000:Monocytes / Q000276:immunology / Q000473:pathology*
D015214:Antigens, Differentiation, Myelomonocytic