L-selectin mediates downregulation of neutrophil TNF receptors.
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.
Richter
J
J
Department of Medicine, University Hospital, Lund, Sweden.
Zetterberg
E
E
D015703:Antigens, CD / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology; D002118:Calcium / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015536:Down-Regulation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019041:L-Selectin; D009504:Neutrophils / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D015815:Cell Adhesion Molecules; D018124:Receptors, Tumor Necrosis Factor; D063268:Sialic Acid Binding Ig-like Lectin 3; D019041:L-Selectin; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium