The CXC Chemokines Growth-regulated Oncogene (GRO) α, GROβ, GROγ, Neutrophil-activating Peptide-2, and Epithelial Cell-derived Neutrophil-activating Peptide-78 Are Potent Agonists for the Type B, but Not the Type A, Human Interleukin-8 Receptor

摘要: Interleukin-8 (IL-8), growth-related oncogene (GRO) α, GROβ, GROγ, neutrophil-activating peptide-2 (NAP-2), epithelial cell-derived neutrophil activating peptide- 78 (ENA-78), and granulocyte chemoattractant protein-2 are potent chemoattractants 40-90% identical in amino acid sequence that comprise a subgroup of human CXC chemokines defined by the conserved motif glutamic acid-leucine-arginine (ELR). Two chemotactic receptor subtypes for IL-8, named IL-8 receptors (IL8R) A B, have been cloned. They 78% sequence, coexpressed neutrophils, distinguished their different selectivities GROα NAP-2. Their selectivity other ELR+ has not previously reported. By measuring calcium flux embryonic kidney 293 cells transfected with plasmids encoding IL8RA or IL8RB, we now ENA-78. The rank order agonist potency, based on inspection mean effective concentration values (EC50), IL8RB was GROγ (1 nM) > (4 ∼ (5 GROβ NAP-2 (7 ENA-78 (11 nM), >>> (40 (45 (63 nM)∼GROγ (65 GROβ. maximal response to at least 2-fold greater than five chemokines. All six agonists competed high affinity 125I-IL-8, -GROα, -NAP-2, -ENA-78 binding sites IL8RB. GROα, NAP-2, weakly site IL8RA. Thus, both highly selective similar sequences but differ dramatically all tested. These findings important implications developing novel neutrophil-specific anti-inflammatory drugs directed against chemokine signaling system.