Abstract
In this study, rat neutrophils and macrophages produced cytokine-induced neutrophil chemoattractants (CINCs) and rat macrophage inflammatory protein-1α (MIP-lα) in different patterns during phagocytosis of heat-killed yeast cells in vitro. The cultured supernatants of the phagocytosing rat neutrophils and macrophages had chemotactic activities toward neutrophils, and the chemotactic potencies were markedly inhibited by anti-CINCs IgGs or/and anti-MIP-lα IgG, suggesting that CINCs and MIP-lα are major neutrophil chemoattractants produced by the phagocytosing neutrophils and macrophages. Dexamethasone suppressed the production of CINCs and MIP-1α by the phagocytosing cells in a dose-dependent manner. Our results demonstrate significant differences in the production of CINCs and MIP-1α by neutrophils and macrophages during phagocytosis of yeast cells and thus may suggest the different contribution of each chemokine to neutrophil recruitment in the processes of inflammation in rats.
Similar content being viewed by others
REFERENCES
Kennedy, J., G. S. Kelner, S. Kleyensteuber, T. J. Schall, M. C. Weiss, H. Yssel, P. V. Scheider, B. G. Cocks, K. B. Bacon, and A. Zlotnik. 1995. Molecular cloning and functional characterization of human lymphotactin. J. Immunol. 155:203–209.
Wells, T. N. C., and M. C. Peitsch. 1997. The chemokine information source-identification and characterization of novel chemokines using the worldwideweb and expressed sequence TAG databases. J. Leukocyte Biol. 61:545–550.
Nakagawa, H., N. Komorita, F. Shibata, A. Ikesue, K. Konishi, M. Fujioka, and H. Kato. 1994. Identification of cytokine-induced neutrophil chemoattractants (CINC), rat GRO/CINC-2α and CINC-2β, produced by granulation tissue in culture: purification, complete amino acid sequences and characterization. Biochem. J. 301:545–550.
Shibata, F., K. Konishi, H. Kato, N. Komorita, M. Al-Mokdad, M. Fujioka, and H. Nakagawa. 1995. Recombinant production and biological properties of rat cytokine-induced neutrophil chemoattractants, GRO/CINC-2α, CINC-2β and CINC-3. Eur. J. Biochem. 231:306–311.
Al-mokdad, M., F. Shibata, and H. Nakagawa. 1997. Effect of cytokine-induced neutrophil chemoattractants (CINCs) on shape change, adhesiveness and phagocytosis of rat neutrophils. Biol. Pharm. Bull. 20:920–923.
Al-mokdad, M., F. Shibata, and H. Nakagawa. 1996. Evidence for two putative receptors mediating chemotactic activity of cytokine-induced neutrophil chemoattractants (CINCs) for rat neutrophils. Biol. Pharm. Bull. 19:879–881.
Nakagawa, H., S. Shiota, K. Takano, F. Shibata, and H. Kato. 1996. Cytokine-induced neutrophil chemoattractant (CINC)-2α, a novel member of rat GRO/CINCs, is a predominant chemokine produced by lipopolysaccharide-stimulated rat macrophages in culture. Biochem. Biophys. Res. Commun. 220:945–948.
Shanley, T. P., H. Schmal, H. P. Friedl, M. L. Jones, and P. A. Ward. 1995. Role of macrophage inflammatory protein-1α (MIP-1α) in acute lung injury in rats. J. Immunol. 154:4793–4802.
Nakagawa, H., A. Ikesue, H. Kato, H. Debuchi, K. Watanabe, S. Tsurufuji, M. Naganawa, M. Mitamura. 1992. Changes in the level of rat interleukin 8/CINC and gelatinase in the exudate of carrageenin-induced inflammation in rats. J. Pharmacobio-Dyn. 15:461–466.
Shibata, F., H. Kato, K. Konishi, A. Okumura, H. Ochiai, K. Nakajima, M. Al-Mokdad, and H. Nakagawa. 1996. Differential changes in the concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in exudate during rat lipopolysaccharide-induced inflammation. Cytokine 8:222–226.
Watanabe, K., K. Kinoshita, and H. Nakagawa. 1989. Very rapid assay of polymorphonuclear leukocyte chemotaxis in vitro. J. Pharmacol. Methods 22:13–18.
Baggiolini, M., and B. Dewald. 1984. Exocytosis by neutrophils. Contemp. Top. Immunobiol. 14:221–226.
Rossi, F. 1986. The O −2 forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochem. Biophys. Acta. 853:65–89.
Claesson, H. E., U. Lundberg, and C. Malmsten. 1981. Serum-coated zymosan stimulates the synthesis of leukotriene B4 in human polymorphonuclear leukocytes. Inhibition by cyclic AMP. Biochem. Biophys. Res. Commun. 99:1230–1237.
Sanchez Crespo, M., F. Alonso, and J. Egido. 1980. Platelet-activating factor in anaphylaxis and phagocytosis. I. Release from human peripheral polymorphonuclears and monocytes during the stimulation by ionophore A23187 and phagocytosis but not from degranulation basophils. Immunology 40:645–655.
Dubravec, D. B., D. R. Spriggs, J. A. Mannick, and M. L. Rodrick. 1990. Circulating human peripheral blood granulocytes synthesize and secrete tumor necrosis factor α. Proc. Natl. Acad. Sci. U.S.A. 87:7658–7661.
Tiku, K., M. L. Tiku, and J. L. Skosey. 1986. Interleukin 1 production by human polymorphonuclear neutrophils. J. Immunol. 136:3677–3685.
Cicco, N. A., A. Lindemann, J. Content, P. Vandenbussche, M. Lubbert, M. J. Gauss, R. Mertelsman, and F. Herrman. 1990. Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α. Blood 10:2049–52.
Lindemann, A., D. Riedel, W. Oster, H. W. Zielgler-Heitbrock, R. Mertelsmann, and F. Herrman. 1989. Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes. J. Clin. Invest. 83:1308–1312.
Shirafuji, N., S. Matsuda, H. Ogura, K. Tani, H. Kodo, K. Ozawa, S. Nagata, S. Asano, and F. Takaku. 1990. Granulocyte colony-stimulating factor stimulates human mature neutrophilic granulocytes to produce interferon-α. Blood 75:17–19.
Bazzoni, F., M. A. Cassatella, F. Rossi, M. Ceska, B. Dewald, and M. Baggiolini. 1991. Phagocytosis neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J. Exp. Med. 173:771–774.
Strieter, R. M., K. Kashahara, R. Allen, H. J. Showell, T. J. Standiford, and S. L. Kunkel. 1990. Human neutrophils exhibit disparate chemotactic factor gene expression. Biochem. Biophys. Res. Commun. 173:725–730.
Knudsen, P. J., C. A. Dinarello, and T. B. Strom. 1987. Glucocorticoids inhibit transcriptional and post-transcriptional expression of interleukin 1 in U937 cell. J. Immunol. 139:4129–4134.
Beutler, B., N. Krochin, I. W. Milsark, C. Lueke, and A. Cerami. 1986. Control of Cachectin (tumor necrosis factor) synthesis: mechanism of endotoxin resistance. Science 232:977–980.
Amon, Y., S. W. Lee, and A. C. Allison. 1993. Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability. Mol. Pharmacol. 43:176–182.
Mukaida, N., M. Shiroo, and K. Matsushima. 1989. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J. Immunol. 143:1366–1371.
Mukaida, N., C. C. O. Zachariae, G. L. Gusella, and K. Matsushima. 1991. Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. J. Immunol. 146:1212–1215.
Nakagawa, H., A. Ikesue, S. Hatakeyama, H. Kato, T. Gotoda, N. Komorita, K. Watanabe, and H. Miyai. 1993. Production of an interleukin-8-like chemokine by cytokine-stimulated rat NRK-49F fibroblasts and its suppression by anti-inflammatory steroids. Biochem. Pharmacol. 45:1425–1430.
Ohtsuka, T., A. Kubota, T. Hirano, K. Watanabe, H. Yoshida, M. Tsurufuji, Y. Iizuka, K. Konishi, and S. Tsurufuji. 1996. Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil chemoattractant CINC/gro, a member of the interleukin-8 family, through impairment of NF-κB activation. J. Biol. Chem. 271:1651–1659.
Blondin, J., and A. Janoff. 1976. The role of lysosomal elastase in the digestion of Escherichia coli proteins by human polymorphonuclear leukocytes. J. Clin. Invest. 58:971–979.
Janoff, A., and J. Scherer. 1968. Mediators of inflammation in leukocyte lysosomes. IX. Elastolytic activity in granules of human polymorphonuclear leukocytes. J. Exp. Med. 128:1137–1155.
Lazarus, G., J. Daniels, R. Brown, and H. Bladen. 1968. Degradation of collagen by a human collagenolytic system. J. Clin. Invest. 47:2622–2628.
Ohlsson, K., and J. Olsson. 1973. The neutral proteases of human granulocytes. Isolation and partial characterization of two granulocyte collagenases. Eur. J. Biochem. 36:473–481.
Bretz, U., and M. Baggiolini. 1974. Biochemical and morphological characterization of azurophil and specific granules of human neutrophilic polymorphonuclear leukocytes. J. Cell Biol. 63:251–269.
Murphy, G., J. J. Reynolds, U. Bretz, and M. Baggiolini. 1977. Collagenase is a component of the specific granules of human neutrophil leukocytes. Biochem. J. 162:195–197.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Al-Mokdad, M., Shibata, F., Takano, K. et al. Differential Production of Chemokines by Phagocytosing Rat Neutrophils and Macrophages. Inflammation 22, 145–159 (1998). https://doi.org/10.1023/A:1022383922039
Issue Date:
DOI: https://doi.org/10.1023/A:1022383922039