Functional expression of the CD163 scavenger receptor on acute myeloid leukemia cells of monocytic lineage.
The hemoglobin-haptoglobin (Hb-Hp) scavenger receptor CD163 is a monocyte/macrophage-restricted surface antigen, whose expression is strongly up-regulated by glucocorticoids. We have previously shown that CD163 is expressed by acute myeloid leukemia (AML) cells of monocytic lineage. Herein, we expand this finding by demonstrating constitutive and glucocorticoid-enhanced CD163 expression on French-American-British M4/M5 AML cells, and leukemic blasts of other AML subtypes and normal hematopoietic progenitor cells do not express CD163. We provide evidence that the functional characteristics of CD163 are preserved on malignant cells by showing the capability of types M4/M5 blast cells to internalize Hb-Hp by a CD163-mediated mechanism. Together, our results identify CD163 as a potential target for therapeutic intervention. It is important that CD163 does not appear to be released from leukemic blasts under noninflammatory conditions, thus reducing the probability of off-target side-effects as a result of competitive binding of potential therapeutic ligands to nonmembrane-bound CD163.
Bächli
Esther B
EB
Department of Medicine, University Hospital of Zürich, CH-8091 Zürich, Switzerland. klinsog@usz.unizh.ch.
Schaer
Dominik J
DJ
Walter
Roland B
RB
Fehr
Jörg
J
Schoedon
Gabriele
G
D000208:Acute Disease; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006242:Haptoglobins / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006454:Hemoglobins / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D005938:Glucocorticoids; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface