Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on chronic lymphocytic leukaemia cells.
Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion receptors which are involved include CD44 and the integrin family, CD11/CD18. In this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for the expression of these adhesion molecules, and for the way in which cytokines are able to modulate the levels of these receptors. B-CLL cells express significant but variable levels of LAM-1 and high levels of CD44. In contrast, these cells exhibit very low or absent amounts of surface CD11a, CD11b, or CD11c. Most CLL cells expressed no detectable levels of intercellular adhesion molecule-1 but some cases show levels of up to 30%. Following 24 h incubation with interferon alpha (500 U/ml), surface LAM-1 expression on peripheral blood E-negative cells from CLL patients rose to 330 +/- 127% of levels on control cells incubated with medium alone (n = 13, p less than 0.0005). Interleukin 4 (1 ng/ml) and interferon gamma (100 U/ml) also increased surface LAM-1 levels on these cells to 218 +/- 119% (n = 8, p less than 0.001) and 245 +/- 116% (n = 5, p less than 0.001) of control levels respectively. Induction of LAM-1 expression occurred over 48 h (greater than 50% of the increase was seen in the first 24 h) in a dose-dependent manner and required protein synthesis. The induction of LAM-1 expression on the malignant cells may, by altering the homing behaviour of these cells, relate to the reduction in peripheral leukaemic cells seen following treatment with interferon alpha in CLL.
Jewell
A P
AP
Department of Haematology, University College and Middlesex School of Medicine, London, UK.
Yong
K L
KL
Worman
C P
CP
Giles
F J
FJ
Goldstone
A H
AH
Lydyard
P M
PM
D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D019041:L-Selectin; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D007371:Interferon-gamma