Down-regulation by tumor necrosis factor-alpha of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism.
Adhesion of human neutrophils to endothelial cells is a crucial step during migration to the extravascular sites of inflammation. A large number of molecules, including the CD44 and LAM-1 antigens, have been described to participate in this process. We have investigated the regulation by human recombinant tumor necrosis factor-alpha (TNF-alpha) of human neutrophil plasma membrane expression of both CD44 and LAM-1 adhesion molecules, as well as that of CD43 sialophorin, which has been involved in adhesion and activation of leukocytes. The expression of these three antigens was down-regulated in neutrophils upon TNF-alpha treatment, as determined by immunofluorescence and immunoprecipitation experiments. However, the expression of other cell surface molecules, such as CD45 or CD11b, was up-regulated. Similar regulatory effects were also observed upon neutrophil treatment with other activating agents such as the chemoattractant peptide formyl-Met-Leu-Phe, the calcium ionophore A23187, or the phorbol ester phorbol 12-myristate 13-acetate. Protease inhibitors virtually abrogated the TNF-alpha-induced down-regulation of CD43 and CD44 expression, but not that of LAM-1, suggesting the involvement of a protease activity in this process. These results underline the role of TNF-alpha on the differential regulation of cell surface expression of neutrophil adhesion molecules, thus implying modifications in the neutrophil adhesive properties.
Campanero
M R
MR
Sección de Inmunologia, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
Pulido
R
R
Alonso
J L
JL
Pivel
J P
JP
Pimentel-Muiños
F X
FX
Fresno
M
M
Sánchez-Madrid
F
F
D015703:Antigens, CD / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D051917:Leukosialin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D011233:Precipitin Tests; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D006649:Histocompatibility Antigens; D051917:Leukosialin; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate