Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils.
The regulation of monocyte-derived neutrophil chemotactic factor (MDNCF)/interleukin 8 (IL 8) receptor expression by the MDNCF/IL 8 ligand was examined using freshly isolated human peripheral blood neutrophils. MDNCF/IL 8 down-regulated greater than 90% of its own receptor expression within 10 min at 37 degrees C. This down-regulation was associated with internalization of the ligand. The radiolabeled MDNCF/IL 8 molecules after internalization were proteolytically degraded, and trichloroacetic acid-soluble molecules were released into the culture medium starting at 60 min. Lysosomotropic agents could inhibit this degradation of ligand suggesting the involvement of lysosomal enzymes in this proteolytic digestion. MDNCF/IL 8 receptors reappeared on the cell surface within 10 min after removal of free ligands from the culture medium. Cycloheximide did not alter the reappearance of the receptor suggesting that de novo protein synthesis of MDNCF/Il 8 receptors is not involved in this event and that receptors probably recycled. The addition of lysosomotropic agents partially inhibited the reappearance/recycling of the receptors, although none of these agents inhibited the binding of ligand to the surface receptors or ligand internalization. Ammonium chloride reduced the MDNCF/IL 8-induced neutrophil chemotactic response in a dose-dependent fashion. These data suggest that MDNCF/IL 8 receptor expression is dynamically regulated by MDNCF/IL 8 and that the rapid recycling of MDNCF/IL 8 receptors may be essential for the chemotactic response of neutrophils.
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland 21701-1013.
A K
AK
Samanta
J J
JJ
Oppenheim
K
K
Matsushima
D000643:Ammonium Chloride / Q000494:pharmacology; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism* / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D016209:Interleukin-8; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*
D002630:Chemotactic Factors; D016209:Interleukin-8; D007378:Interleukins; D000643:Ammonium Chloride; C008542:monodansylcadaverine; D002103:Cadaverine