GRANULOCYTE-COLONY-STIMULATING FACTOR AND LIPOPOLYSACCHARIDE REGULATETHE EXPRESSION OF INTERLEUKIN-8 RECEPTORS ON POLYMORPHONUCLEAR LEUKOCYTES

Interleukin 8 (IL-8) is a potent chemoattractant and activating factor for human polymorphonuclear leukocytes (PMN) and hence plays a critic al role in the pathogenesis of acute inflammation, Two unique but homo logous receptors for IL-8 have been cloned (IL-8RA and -B), each of wh ich binds the IL-8 ligand with high affinity, PMN stimulated by cytoki nes or lipopolysaccharide (LPS) exhibit changes in IL-8R mRNA and I-12 5-IL-8 binding, Granulocyte-colony stimulating factor (G-CSF) treatmen t of PMN enhances, and LPS inhibits, IL-8R mRNA expression, Similarly, I-125-IL-8 ligand binding to PMN is increased by G-CSF and decreased by LPS treatment, The stimulatory effect of G-CSF on IL-8R expression is transcriptional as it is inhibited by actinomycin D and is evident in nuclear run-on analyses. In contrast, LPS down-regulates IL-8R by b oth transcriptional and post-transcriptional mechanisms. The alteratio ns in IL-8R expression are associated with similar changes in the IL-8 -induced chemotactic responses of PMN. In conclusion, the two types of IL-8 receptor differ in their cellular distribution and are regulated in response to cytokines and LPS, Regulation of IL-8R expression by e ndogenous and exogenous immunomodulators may be important in the in vi vo control of PMN effector functions in inflammation.