Defective monocyte-to-macrophage maturation in patients with aplastic
anemia
R Andreesen, W Brugger, C Thomssen, A Rehm, B Speck and GW Lohr
Department for Hematology and Oncology, Albrecht-Ludwigs-Universitat
Freiburg i. Brsg., FRG.
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.
Volume 74,
Issue 6,
pp. 2150-2156,
11/01/1989
Copyright © 1989 by The American Society of Hematology
