Constitutive expression of interleukin-8 and its receptor in human myeloid and lymphoid leukemia.
Interleukin-8 (IL-8), a member of the family of small inducible cytokines, is mainly known for its striking neutrophil-activating properties. Constitutive IL-8 production is negligible in normal leukocytes. We examined expression of IL-8 and its receptor in purified leukemic cells from patients with untreated acute myeloblastic leukemia (AML) and lymphoid leukemias. In the majority of cases (18 of 26 AML, 8 of 15 lymphoid leukemias), the cells constitutively expressed IL-8 mRNA transcripts. In all but 3 of these cases, IL-8 mRNA-expressing cells secreted biologically active IL-8 protein. Immunocytochemical analysis showed intracellular IL-8 (5% to 90% of total cells), demonstrating that the leukemic cells themselves rather than contaminants (monocytes or lymphocytes) were the source of IL-8. Ten of 25 AML samples expressed IL-8 receptor mRNA and, with 1 exception, the IL-8 receptor expressing cells also produced its ligand. In contrast, all lymphoid leukemias were negative. Furthermore, frequent coexpression of IL-8 and IL-1 beta transcripts was seen in both AML and lymphoid leukemia samples, whereas fewer cases coexpressed IL-8 and either macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor. In leukemic cells expressing the IL-8 receptor, IL-8 induced cytosolic free calcium changes, indicating activation of the classical signaling pathway. These results suggest that IL-8 may have biologic activities in hematopoiesis.
Central Hematology Laboratory, Theodor-Kocher-Institute, University of Berne, Switzerland.
A
A
Tobler
B
B
Moser
B
B
Dewald
T
T
Geiser
H
H
Studer
M
M
Baggiolini
M F
MF
Fey
D015139:Blotting, Southern; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D023062:Receptors, Interleukin-8A; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A