Neutrophilia and B-Cell Plasmacytosis in Mice Lacking the Murine IL-8 Receptor Homolog
Interleukin-8 (IL-8) is a member of a family of proinflammatory cytokines containing four conserved cysteine residues that are related by a C-X-C motif, and is a major factor in acute inflammation, being responsible for the activation and chemotaxis of neutrophils to the site of acute injury (1–5). Neutrophils provide the first line of defense in fighting infection by destroying bacteria with phagocytosis and the release of super oxides and peroxides. The response is rapid and is neither acquired nor antigen specific (6,7). With sepsis or trauma, this usually beneficial response can result in death since an excess of activated neutrophils can produce extensive organ and tissue damage. IL-8 is produced by a large variety of cell types in vitro and has been implicated in neutrophil migration and, to a lesser extent, T-cell migration, to sites of IL-8 injection (8–10). Despite rapid advances in the chemokine field, there has been some frustration in developing small animal models of IL-8 mediated inflammation as neither mouse nor rat IL-8 has been identified (11). Reports that anti-human IL-8 antibodies inhibit lung inflammation in rats (12) suggest the presence of a similar molecule in rodents. Because of the tremendous importance of this molecule in humans, dogs, and rabbits, it is likely that if there is not a murine equivalent of IL-8 then other factor(s) must mediate similar physiological events.
KeywordsNeutrophil Migration Embryonic Stem Cell Clone Neutrophil Production Medullary Cord Mouse Neutrophil
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- 11.Watanabe, K., lida, M., Takaishi, K., Suzuki, T., Hamada, Y., lizuka, Y., and Tsurufuji, S. (1993) Chemoattractants for neutrophils in lipopolysaccharideinduced inflammatory exudate from rats are not interleukin-8 counterparts but gro-gene-product/melanoma-growth-stimulating-activity-related factors. Eur. J. Biochem. 214, 267–270.PubMedCrossRefGoogle Scholar
- 15.Lec, J., Horuk, R., Rice, G. C., Bennett, G. L., Camerato, T., and Wood, W. I. (1992) Characterization of two high affinity human interleukin-8 receptors. J. Biol. Chem. 267, 16283–16287.Google Scholar
- 17.Cerretti, D. P., Nelson, N., Kozlosky, C. J., Morrissey, P. J., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Dosik, J. K., and Mock, B. A. (1993) The murine homologue of the human interleukin-8 receptor type B maps near the Ity-Lsh-Bcg disease resistance locus. Genomics 18, 410–413.PubMedCrossRefGoogle Scholar
- 18.Bozic, C. R., Gerard, N. P., von Uexkull-Guldenband, C., Kolakowski, L. F., Conklyn, M. J., Breslow, R., Showell, H. J., and Gerard, C. (1994) The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. J. Biol. Chem. 269, 29,355–29, 358.Google Scholar
- 22.Watanabe, K., Konishi, K., Fujioka, M., Kinosha, S., and Nakagawa, H. (1989) The neutropil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein. J. Biol. Chem. 264, 19,559–19, 563.Google Scholar
- 23.Kimata, H., Yoshida, A., Ishioka, C., Lindley, I., and Mikawa, H. (1992) Interleukin 8 selectively inhibits immunoglobulin E production induced by IL-4 in human B cells. J. Exp. Med. 176, 1227–1231.Google Scholar