Sodium fluoride reveals multiple pathways for regulation of surface expression of the C3b/C4b receptor (CR1) on human polymorphonuclear leukocytes.
We have examined the effects of NaF on C3b receptor (CR1) expression and function in human polymorphonuclear leukocytes (PMN). Plasma membrane expression of CR1 was determined with a monoclonal antibody (3D9); CR1 function was assessed with erythrocytes bearing C3b (EC3b) or C3b oligomers prepared with avidin and biotin. NaF inhibited in a dose-dependent manner CR1-mediated phagocytosis and NaF inhibited f-met-leu-phe or phorbol dibutyrate-induced increases in CR1 expression, with 50% inhibition at 5 mM NaF. Increased plasma membrane expression of CR3 induced by f-met-leu-phe also was inhibited by NaF. However, increased CR1 and CR3 expression due to incubation at 37 degrees C were unaffected by 10 mM NaF. Incubation of PMN with 10 mM NaF depleted 80% of intracellular adenosine triphosphate (ATP) after 10 min. However, inhibition of CR1 function was unrelated to ATP level, inasmuch as normal increases in CR1 expression and in phagocytosis occurred 20 min after removal of NaF, whereas ATP levels remained below 25% of normal. Strikingly, internalization of soluble oligomeric C3b ligands was unaffected by 10 mM NaF, which completely inhibited phorbol dibutyrate-induced CR1 internalization and EC3b phagocytosis. We conclude that there are two different mechanisms for increasing plasma membrane expression of CR1, one of which is inhibitable by NaF. Moreover, there are two distinct pathways of CR1 internalization which can also be distinguished by their sensitivity to NaF.
D000255:Adenosine Triphosphate / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D011951:Receptors, Complement / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017463:Receptors, Complement 3b; D012969:Sodium Fluoride / Q000494:pharmacology*
D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride