Defective monocyte-to-macrophage maturation in patients with aplastic anemia

Abstract

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.

Characterization of MAX.3 antigen, a glycoprotein expressed on mature macrophages, dendritic cells and blood platelets: identity with CD84

“…In previous studies, MAX.3 was described as a marker of terminal MAC differentiation (e.g. [7,8,[13][14][15][16]). Earlier results obtained by immunoperoxidase staining could be confirmed by flow cytometry and Northern analysis in the work presented here.…”

“…In the recent years, MAX.3 antibody has been used to analyse MAC differentiation under various conditions and it has emerged that MAX.3 antigen expression is closely linked to the morphological and functional features of mature MAC under a variety of experimental conditions [8,[13][14][15][16] ; the corresponding molecule has not yet been defined. Here we report the biochemical and molecular characterization of the antigen detected by MAX.3 antibody.…”

Characterization of MAX.3 antigen, a glycoprotein expressed on mature macrophages, dendritic cells and blood platelets: identity with CD84

“…In previous studies, MAX.3 was described as a marker of terminal MAC differentiation (e.g. [7,8,[13][14][15][16]). Earlier results obtained by immunoperoxidase staining could be confirmed by flow cytometry and Northern analysis in the work presented here.…”

“…In the recent years, MAX.3 antibody has been used to analyse MAC differentiation under various conditions and it has emerged that MAX.3 antigen expression is closely linked to the morphological and functional features of mature MAC under a variety of experimental conditions [8,[13][14][15][16] ; the corresponding molecule has not yet been defined. Here we report the biochemical and molecular characterization of the antigen detected by MAX.3 antibody.…”

Hepatitis C virus infection in acquired aplastic anemia

“…The high rate of seroconversion among HCV RT-PCR positive patients suggests that humoral immunity may be normal in AA. A number of immunologic abnormalities have been observed in AA patients including decreased numbers of circulating B lymphocytes, increased numbers of activated suppressor/cytotoxic T lymphocytes in the blood, defective macrophage differentiation, and decreased circulating levels of interleukin-1 [12][13][14][15][16][17]. In addition, AA patients often receive immunosuppressive medications as part of their treatment; many of our patients were treated with glucocorticoids prior to their referral.…”