Abstract
In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammutory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4μg/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutroph il infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37δC for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact ruts. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.
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Yoshimura, T., K. Matushima, J. J. Oppenheim, andE. J. Leonard. 1987. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS) -stimulated human blood mononuclear leukocytes: Partial characterization and separation from interleukin 1 (IL 1).J. Immunol. 139:788–793.
Walz, A., P. Peveri, H. Aschauer, andM. Bagoiollini. 1987. Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes.Biochem. Biophys. Res. Commun. 149:755–761.
Tanaka, S., E. A. Robinson, T. Yoshimura, K. Matsushima, E. J. Leonard, andE. Appella. 1988. Synthesis and biological characterization of monocyte-derived neutrophil-chemotactic factor.FEBS Lett. 236:467–470.
Larsen, C. G., A. O. Anderson, E. Appella, J. J. Oppenheim, andK. Matsushima. 1989. The neutrophil-activating protein (NAP-1) is also chemotactic for lymphocytes.Science 243:1464–1466.
Seitz, M., B. Dewald, S. Gerber, andM. Bagoiolini. 1991. Enhancing production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis.J. Clin. Invest. 87:463–469.
Watanabe, K., S. Kinoshita, andH. Nakagawa. 1989. Purification and characterization of cytokine-induced neutrophil chemoattractant produced by epithelioid cell line of normal rat kidney (NRK-52E cell).Biochem. Biophys. Res. Commun. 161:1093–1099.
Watanabe, K., K. Konishi, M. Fujioka, S. Kinoshita, andH. Nakagawa. 1989. The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein.J. Biol. Chem. 264:19559–19563.
Matsushima, T., K. Morishita, T. Yoshimura, S. Levu, Y. Kobayashi, W. Lee, E. Appella, H. F. Kung, E. J. Leonard, andJ. J. Oppenheim. 1988. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumoenecrosis factor.J. Exp. Med. 167:1883–1893.
Rampart, M., J. Van Damme, L. Zonnekeyn, andA. G. Herman. 1989. Granulocyte chemotactic protein/interleukin-8 induces plasma leakage and neutrophil accumulation in rabbit skin.Am. J. Pathol. 135:21–25.
Larsen, C. G., A. O. Anderson, J. J. Oppenheim, andK. Matsushima. 1989. Production of interleukin-8 by human dermal flbroblasts and keratinocytes in response to interleukin-1 or tumor necrosis factor.Immunology 68:31–36.
Mukaida, N., M. Shiroo, andK. Matsushima. 1989. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.J. Immunol. 143:1366–1371.
Watanabe, K., andH. Nakagawa. 1990. Cytokines enhance the production of a chemotactic factor for polymorphomiclear leukocytes by rat renal glomerular epithelioid cells.Nephron 54:169–175.
Fradin, A., B. Rothhut B. Poincelot-Canton, M. Errasfa, andF. Russo-Marie. 1988. Inhibition of eicosanoid and PAF formation by dexamethasone in rat inflammatory polymor-phonuclear neutrophils may implicate lipocortin‘s’.Biochim. Biophys. Acta 963:248–257.
Watanabe, M., M. Yagi, M. Omata, N. Hirasawa, S. Mue, S. Tsurufuji, andK. Ohuchi. 1991. Stimulation of neutrophil adherence to vascular endothelial cells by histamine and thrombin and its inhibition by PAF antagonists and dexamethasone.Br. J. Pharmacol. 102:239–245.
Kurihara, A., F. Ojima. andS. Tsurufuji. 1984. Analysis of the effects of an antiinffammatory steroid, dexamethasone, on neutrophil chemotaxis in the Boyden chamber with a modified51Cr-labeling method.J. Pharmacobio. Dyn. 7:742–754.
Watanabe, K., H. Nakagawa, andS. Tsurufuji. 1985. A new simple plastic chemotaxis device of the Boyden chamber type utilizing an immunoassay plate.Jpn. J. Pharmacol. 39:102–104.
Deuel, T. F., R. M. Senior, D. Chang, G. L. Griffin, R. L. Heinrikson, andE. T. Kaiser. 1981. Platelet factor 4 is chemotactic for neutrophils and monocytes.Proc. Natl. Acad. Sci. U.S.A. 78:4584–4587.
Lindley, L, H. Aschauer, J.-M. Seifert, C. Lam, W. Brunowsky, E. Kownatzki, M. Thelen, P. Peveri, B. Dewald, V. von Tscharner, A. Walz, andM. Baggiolini. 1988. Synthesis and expression inEscherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: Biological equivalence between natural and recombinant neutrophil-activating factor.Proc. Natl. Acad. Sci. U.S.A. 85:9199–9203.
Tsurufuji, S., A. Kurihara, andF. Ojima. 1984. Mechanisms of anti-inflammatory action of dexamethasone: Blockade by hydrocortisone mesylate and actinomycin D of the inhibitory effect of dexamethasone on leukocyte infiltration in inflammatory sites.J. Pharmacol. Exp. Ther. 229:237–243.
Miyasaka, K., andT. Mikami. 1982. Comparison of the antiinflammatory effects of dexa-methasone, indomethacin and BW 755c on carrageenin-induced pleurisy in rats.Eur. J. Pharmacol. 77:229–236.
Tsurufuji, S., A. Kurihara, S. Kiso, Y. Suzuki, andK. Ohuchi. 1984. Dexamethasone inhibits generation in inflammatory sites of the chemotactic activity attributable to leukotriene B4.Biochem. Biophys. Res. Commun. 119:884–890.
Schroder, J.-M. 1989. The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate.J. Exp. Med. 170:847–863.
Carveth, H. J., J. F. Bohnsack, T. M. McIntyre, M. Baggiolini, S. M. Prescott, andG. A. Zimmerman. 1989. Neutrophil activating factor (NAF) induces polymorphonuclear leukocyte adherence to endothelial cells and to subendothelial matrix protein.Biochem. Biophys. Res. Commun. 162:387–393.
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Hirasawa, N., Watanabe, M., Mue, S. et al. Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats. Inflammation 16, 187–196 (1992). https://doi.org/10.1007/BF00918958
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DOI: https://doi.org/10.1007/BF00918958