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.
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.
Loetscher
P
P
Theodor-Kocher Institute, University of Bern, Switzerland.
Seitz
M
M
Clark-Lewis
I
I
Baggiolini
M
M
Moser
B
B
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers; D006133:Growth Substances / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000502:physiology*; D051381:Rats; D018123:Receptors, Interleukin / Q000502:physiology*; D023062:Receptors, Interleukin-8A; D014162:Transfection; D014407:Tumor Cells, Cultured; D001620:beta-Thromboglobulin
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D017931:DNA Primers; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; C061615:PPBP protein, human; D010455:Peptides; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D001620:beta-Thromboglobulin; C009862:connective tissue-activating peptide; D002118:Calcium