CDB15:0001247 PPBP — CXCR1
Experimentally validated in Human; Orthology-inferred in Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Cow, Chimp, Horse, Marmoset
Title
Journal:; Year Published:
Abstract
Both interleukin-8 receptors independently mediate chemotaxis. Jurkat cells transfected with IL-8R1 or IL-8R2 migrate in response to IL-8, GRO alpha and NAP-2.
FEBS letters, 1994; PubMed, Homo sapiens PPBP — Homo sapiens CXCR1
ABSTRACT: Neutrophil leukocytes, the target cells for interleukin-8 and related CXC chemokines, bear high numbers of two types of IL-8 receptors (IL-8R1 and IL-8R2). By cDNA transfection Jurkat cell lines were generated that stably express either IL-8R1 or IL-8R2 (J-IL8R1 and J-IL8R2). J-IL8R1 expressed 4,000 +/- 1,000 copies of IL-8R1, and bound IL-8 with high affinity (Kd 1-4 nM) and GRO alpha and NAP-2 with low affinity (Kd 200-500 nM). J-IL8R2 expressed 17,000 +/- 3,000 copies of IL-8R2, and bound all three chemokines with high affinity. Both transfectants showed a similar degree of chemotactic migration after stimulation with IL-8, GRO alpha and NAP-2. All three chemokines were equally potent as attractants of J-IL8R2, whereas IL-8 was 300 to 1,000-fold more potent than GRO alpha or NAP-2 as attractant of J-IL8R1. The potencies, therefore, agree with the affinities of the ligands to IL-8R1 and IL-8R2. Our results demonstrate that both IL-8 receptors function independently, and mediate chemotaxis in response to IL-8 and other CXC chemokines.
The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2.
Blood, 1997; PubMed, Homo sapiens PPBP — Homo sapiens CXCR1
ABSTRACT: The CXC-chemokines interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2), and melanoma growth-stimulatory activity (MGSA) are chemoattractants with high selectivity for neutrophils. Although IL-8 has been shown to act as an extremely potent mediator, reports on NAP-2 and MGSA are still contradictory. Here we show for the first time that NAP-2 and MGSA induce two distinct optima of neutrophil chemotaxis. A first optimum is elicited within a concentration range as low as it is characteristic for IL-8. However, a second optimum appears at more than 200-fold higher stimulus concentrations, at which IL-8 is inactive. Investigating the involvement of the two chemokine receptors CXCR-1 and CXCR-2 in NAP-2-mediated chemotaxis, we observe that the cells become desensitized to the first optimum of the chemokine after selective downregulation of CXCR-2, while both optima disappear upon simultaneous downregulation of both receptors. Blocking monoclonal antibodies (MoAbs) specific for CXCR-2 or CXCR-1 either suppress the first optimum of NAP-2-induced chemotaxis or drastically reduce the second one, respectively. These results provide evidence that both receptors are involved in NAP-2-induced neutrophil chemotaxis, with CXCR-2 rendering the cells responsive to low dosages of the chemokine, and with CXCR-1 extending their responsiveness to NAP-2 dosages higher by several orders of magnitude.