The Journal of Immunology, Vol 149, Issue 8 2662-2667, Copyright © 1992 by American Association of Immunologists

ARTICLES

Activation of human basophils through the IL-8 receptor

M Krieger, T Brunner, SC Bischoff, V von Tscharner, A Walz, B Moser, M Baggiolini and CA Dahinden
Institute of Clinical Immunology, University of Bern, Switzerland.

IL-8 and its structural analogs derived from blood platelets have been proposed as stimuli of IgE-independent basophil activation. In order to clarify the mechanism of action of these peptides, we examined the effects of pure IL-8, connective tissue-activating peptide III (CTAP- III), neutrophil-activating peptide 2 (NAP-2), and platelet factor 4 (PF-4) on blood basophils with and without pretreatment by IL-3, which modulates mediator release. After pretreatment with IL-3, significant histamine release was observed with 10(-8) M and 10(-7) M IL-8 and 10(- 7) M NAP-2, but not with the other peptides. At higher concentrations (10(-6) M), however, all IL-8 analogs, as well as the unrelated cationic peptides poly-D-lysine, histone VS, and lysozyme, induced histamine release to variable degrees. Binding and competition studies with [125I]IL-8 revealed specific IL-8R on basophils from a patient with chronic myelogenous leukemia and normal individuals. From 3500 to 9600 receptors with a mean Kd value of 0.15 nM were found on average per chronic myelogenous leukemia and normal basophil, respectively. NAP- 2 weakly competed for IL-8 binding. IL-8 and, to a lesser extent, NAP-2 led to a transient rise of cytosolic free calcium concentration ([Ca2+]i), which was independent of a preexposure to IL-3. IL-8 prevented the [Ca2+]i rise induced by NAP-2, but did not influence [Ca2+]i responses to other agonists, e.g. C5a, C3a, or platelet- activating factor. IL-8 induced [Ca2+]i changes and histamine release in IL-3-primed basophils were pertussis toxin sensitive. CTAP-III or PF- 4 did not compete for IL-8 binding, did not induce [Ca2+]i changes, and did not influence the [Ca2+]i response to IL-8 and NAP-2. This study shows that IL-8 and NAP-2 activate human basophils by a receptor- mediated mechanism similar to that operating in neutrophils. At high concentrations histamine release can also be induced by cationic peptides by a mechanism that does not involve the IL-8R, and probably depends on cationic interactions.

This article has been cited by other articles:

				A. de Paulis, N. Prevete, I. Fiorentino, A. F. Walls, M. Curto, A. Petraroli, V. Castaldo, P. Ceppa, R. Fiocca, and G. Marone Basophils Infiltrate Human Gastric Mucosa at Sites of Helicobacter pylori Infection, and Exhibit Chemotaxis in Response to H. pylori-derived Peptide Hp(2-20) J. Immunol., June 15, 2004; 172(12): 7734 - 7743. [Abstract] [Full Text] [PDF]

				M. Iikura, M. Miyamasu, M. Yamaguchi, H. Kawasaki, K. Matsushima, M. Kitaura, Y. Morita, O. Yoshie, K. Yamamoto, and K. Hirai Chemokine receptors in human basophils: inducible expression of functional CXCR4 J. Leukoc. Biol., July 1, 2001; 70(1): 113 - 120. [Abstract] [Full Text] [PDF]

				A. Heinemann, A. Hartnell, V. E. L. Stubbs, K. Murakami, D. Soler, G. LaRosa, P. W. Askenase, T. J. Williams, and I. Sabroe Basophil Responses to Chemokines Are Regulated by Both Sequential and Cooperative Receptor Signaling J. Immunol., December 15, 2000; 165(12): 7224 - 7233. [Abstract] [Full Text] [PDF]

				U. Lippert, M. Artuc, A. Grutzkau, A. Moller, A. Kenderessy-Szabo, D. Schadendorf, J. Norgauer, K. Hartmann, R. Schweitzer-Stenner, T. Zuberbier, et al. Expression and Functional Activity of the IL-8 Receptor Type CXCR1 and CXCR2 on Human Mast Cells J. Immunol., September 1, 1998; 161(5): 2600 - 2608. [Abstract] [Full Text] [PDF]

				M. C. Johnson II, O. Kajikawa, R. B. Goodman, V. A. Wong, S. M. Mongovin, W. B. Wong, R. Fox-Dewhurst, and T. R. Martin Molecular Expression of the alpha-Chemokine Rabbit GRO in Escherichia coli and Characterization of Its Production by Lung Cells in Vitro and in Vivo J. Biol. Chem., May 3, 1996; 271(18): 10853 - 10858. [Abstract] [Full Text] [PDF]

				C. A. Power, A. Meyer, K. Nemeth, K. B. Bacon, A. J. Hoogewerf, A. E. I. Proudfoot, and T. N. C. Wells Molecular Cloning and Functional Expression of a Novel CC Chemokine Receptor cDNA from a Human Basophilic Cell Line J. Biol. Chem., August 18, 1995; 270(33): 19495 - 19500. [Abstract] [Full Text] [PDF]