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L‐Selectin mediates downregulation of neutrophil TNF receptors
Author(s) -
Richter Johan,
Zetterberg Eva
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.56.4.525
Subject(s) - receptor , downregulation and upregulation , tumor necrosis factor alpha , biology , integrin , cd18 , microbiology and biotechnology , cell adhesion , e selectin , immunology , cell , biochemistry , gene
Tumor necrosis factor (TNF) is a potent activator of neutrophil granulocytes, which acts via two cell‐surface receptors: the p55‐TNF receptor (TNF‐R55) and the p75‐TNF receptor (TNF‐R75). Proteolytic cleavage of the extracellular region of the receptors results in formation of soluble TNF‐binding proteins, TNF‐R55‐BP and TNF‐R75‐BP. We recently reported that adherence alone, without any further stimuli, causes release of both TNF‐R55‐BP and TNF‐R75‐BP and that both leukocyte‐integrin‐dependent and non‐integrin‐dependent adherence mechanisms can modulate TNF receptor expression. In the present work we show that crosslinking of a mAb to the adhesion protein l‐selectin (TQ1) on the surface of neutrophils results in downregulation of TNF‐receptor binding capacity. Furthermore, when the fluctuations of cytosolic free calcium found in adherent neutrophils were blocked with the cell‐permeable calcium chelator BAPTA, adherence‐induced release of TNF‐R55‐BP was inhibited. We have shown that adherence, via mechanisms involving two adhesion proteins, l‐selectin and the CD11/CD18 leukocyte integrins, and fluctuations of cytosolic free calcium, can result in downregulation of neutrophil TNF‐receptors. J. Leukoc. Biol. 56: 525–527; 1994.