Regulation of leukocyte adhesion molecule-1 (TQ1, Leu-8) expression and shedding by normal and malignant cells.
The human leukocyte adhesion molecule-1 (LAM-1, TQ1, Leu-8) is involved in the binding of human leukocytes to high endothelial venules (HEV) of peripheral lymph nodes (LN). The regulation of LAM-1 expression is unique in that leukocyte stimulation induces a rapid down-modulation of LAM-1 from the cell surface. In this study, the regulation and function of LAM-1 was studied in detail in normal lymphocytes and compared with the LAM-1 of malignant leukocytes. Modulation of LAM-1 from the cell surface occurred concomitantly with the appearance of LAM-1 in the culture medium indicating that LAM-1 is cleaved from the cell surface. Shedding of LAM-1 was decreased in the presence of protein kinase C (PKC) inhibitors. As with normal lymphocytes, cells transfected with the LAM-1 cDNA and chronic lymphocytic leukemia (CLL) cells also shed LAM-1 following phorbol myristate acetate (PMA) exposure. CLL cells expressed the same Mr LAM-1 protein as normal lymphocytes and LAM-1+ CLL cells were able to specifically bind to HEV. In addition, normal lymphocytes and LAM-1+ CLL cells were capable of binding polyphosphomonester core polysaccharide (PPME) derived from yeast cell wall, a carbohydrate which mimics an essential component of the natural ligand for LAM-1, and PPME and HEV binding was specifically blocked by a new monoclonal antibody (mAb) reactive with LAM-1. The expression of LAM-1 and other adhesion molecules was examined on cells of 118 hematopoietic malignancies. LAM-1 was most frequently expressed on CLL and follicular or diffuse small cleaved cell lymphomas, whereas most other malignancies were LAM-1-. Thus, most CLL cells and some non-Hodgkin's lymphoma cells express a functionally active LAM-1 molecule which may correlate with their capacity to migrate through the circulation and disseminate into peripheral LN.
Spertini
O
O
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Freedman
A S
AS
Belvin
M P
MP
Penta
A C
AC
Griffin
J D
JD
Tedder
T F
TF
D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D019041:L-Selectin; D007938:Leukemia / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology*; D011233:Precipitin Tests; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016028:Receptors, Leukocyte-Adhesion; D019041:L-Selectin; D013755:Tetradecanoylphorbol Acetate