TT Kung, DM Stelts, JA Zurcher, GK Adams 3rd, RW Egan, W Kreutner, AS Watnick, H Jones and RW Chapman
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.

Interleukin-5 (IL-5) is important in the control of differentiation, migration, and activation of eosinophils. In order to study the role of IL-5 in the development of eosinophilic inflammation of the airways, we have used a monoclonal antibody to murine IL-5 (TRFK-5) in a murine model of allergic pulmonary inflammation. B6D2F1 mice were sensitized with alum-precipitated ovalbumin and were challenged with aerosolized ovalbumin on day 12 after sensitization. Samples of bronchoalveolar lavage (BAL) fluid, lung tissue, blood, and bone marrow aspirate were collected at different times after ovalbumin challenge. Twenty-four hours after challenge there were significant increases in the number of eosinophils in the BAL fluid, lung tissue, and blood while bone marrow eosinophils were decreased. Treatment of sensitized mice with TRFK-5 (0.01-1 mg/kg, i.p.) 2 h before ovalbumin challenge reduced the numbers of eosinophils in the BAL fluid and lung tissue and prevented the decrease in bone marrow eosinophils in a dose-dependent fashion. The number of eosinophils in the BAL fluid, peribronchial and alveolar regions of the lung was also reduced when TRFK-5 (2 mg/kg, i.p.) was given up to 5 d after ovalbumin challenge. Furthermore, there was no evidence of increased epithelial damage, edema, or the presence of mucus that could have resulted from eosinophil apoptosis and release of toxic proteins after neutralization of IL-5. These results demonstrate an important role for IL-5 in the development of eosinophilic inflammation of the airways and for the migration of eosinophils from the bone marrow into blood in response to antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				D. J. Tumes, J. Cormie, M. G. Calvert, K. Stewart, C. Nassenstein, A. Braun, P. S. Foster, and L. A. Dent Strain-dependent resistance to allergen-induced lung pathophysiology in mice correlates with rate of apoptosis of lung-derived eosinophils J. Leukoc. Biol., June 1, 2007; 81(6): 1362 - 1373. [Abstract] [Full Text] [PDF]

				P. V. Beum, H. Basma, D. R. Bastola, and P.-W. Cheng Mucin biosynthesis: upregulation of core 2 {beta}1,6 N-acetylglucosaminyltransferase by retinoic acid and Th2 cytokines in a human airway epithelial cell line Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L116 - L124. [Abstract] [Full Text] [PDF]

				S.-C. Liao, Y.-C. Cheng, Y.-C. Wang, C.-W. Wang, S.-M. Yang, C.-K. Yu, C.-C. Shieh, K.-C. Cheng, M.-F. Lee, S.-R. Chiang, et al. IL-19 Induced Th2 Cytokines and Was Up-Regulated in Asthma Patients J. Immunol., December 1, 2004; 173(11): 6712 - 6718. [Abstract] [Full Text] [PDF]

				B. Sitkauskiene, A.-K. Johansson, S. Sergejeva, S. Lundin, M. Sjostrand, and J. Lotvall Regulation of Bone Marrow and Airway CD34+ Eosinophils by Interleukin-5 Am. J. Respir. Cell Mol. Biol., March 1, 2004; 30(3): 367 - 378. [Abstract] [Full Text] [PDF]

				C. Buttner, A. Lun, T. Splettstoesser, G. Kunkel, and H. Renz Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions Eur. Respir. J., May 1, 2003; 21(5): 799 - 803. [Abstract] [Full Text] [PDF]

				H. H. Shen, S. I. Ochkur, M. P. McGarry, J. R. Crosby, E. M. Hines, M. T. Borchers, H. Wang, T. L. Biechelle, K. R. O'Neill, T. L. Ansay, et al. A Causative Relationship Exists Between Eosinophils and the Development of Allergic Pulmonary Pathologies in the Mouse J. Immunol., March 15, 2003; 170(6): 3296 - 3305. [Abstract] [Full Text] [PDF]

				J. P. Justice, M. T. Borchers, J. R. Crosby, E. M. Hines, H. H. Shen, S. I. Ochkur, M. P. McGarry, N. A. Lee, and J. J. Lee Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L169 - L178. [Abstract] [Full Text] [PDF]

				J. G. Martin, M. Suzuki, K. Maghni, R. Pantano, D. Ramos-Barbon, D. Ihaku, F. Nantel, D. Denis, Q. Hamid, and W. S. Powell The Immunomodulatory Actions of Prostaglandin E2 on Allergic Airway Responses in the Rat J. Immunol., October 1, 2002; 169(7): 3963 - 3969. [Abstract] [Full Text] [PDF]

				J. R. Crosby, H. H. Shen, M. T. Borchers, J. P. Justice, T. Ansay, J. J. Lee, and N. A. Lee Ectopic expression of IL-5 identifies an additional CD4+ T cell mechanism of airway eosinophil recruitment Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L99 - L108. [Abstract] [Full Text] [PDF]

				T. T. Kung, B. Luo, Y. Crawley, C. G. Garlisi, K. Devito, M. Minnicozzi, R. W. Egan, W. Kreutner, and R. W. Chapman Effect of Anti-mIL-9 Antibody on the Development of Pulmonary Inflammation and Airway Hyperresponsiveness in Allergic Mice Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 600 - 605. [Abstract] [Full Text] [PDF]

				M. Hertz, S. Mahalingam, I. Dalum, S. Klysner, J. Mattes, A. Neisig, S. Mouritsen, P. S. Foster, and A. Gautam Active Vaccination Against IL-5 Bypasses Immunological Tolerance and Ameliorates Experimental Asthma J. Immunol., October 1, 2001; 167(7): 3792 - 3799. [Abstract] [Full Text] [PDF]

				L.-C. Chen, Z. Zhang, A. C. Myers, and S.-K. Huang Cutting Edge: Altered Pulmonary Eosinophilic Inflammation in Mice Deficient for Clara Cell Secretory 10-kDa Protein J. Immunol., September 15, 2001; 167(6): 3025 - 3028. [Abstract] [Full Text] [PDF]

				E. Lach-Trifilieff, R. A. McKay, B. P. Monia, J. G. Karras, and C. Walker In Vitro and In Vivo Inhibition of Interleukin (IL)-5-Mediated Eosinopoiesis by Murine IL-5R{alpha} Antisense Oligonucleotide Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 116 - 122. [Abstract] [Full Text]

				M. Tomaki, L.-L. Zhao, J. Lundahl, M. Sjostrand, M. Jordana, A. Linden, P. O'Byrne, and J. Lotvall Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor {alpha} J. Immunol., October 1, 2000; 165(7): 4040 - 4050. [Abstract] [Full Text] [PDF]

				J. G. Karras, K. McGraw, R. A. McKay, S. R. Cooper, D. Lerner, T. Lu, C. Walker, N. M. Dean, and B. P. Monia Inhibition of Antigen-Induced Eosinophilia and Late Phase Airway Hyperresponsiveness by an IL-5 Antisense Oligonucleotide in Mouse Models of Asthma J. Immunol., May 15, 2000; 164(10): 5409 - 5415. [Abstract] [Full Text] [PDF]

				M. Hojo, M. Suzuki, K. Maghni, Q. Hamid, W. S. Powell, and J. G. Martin Role of Cysteinyl Leukotrienes in CD4+ T Cell-Driven Late Allergic Airway Responses J. Pharmacol. Exp. Ther., May 1, 2000; 293(2): 410 - 416. [Abstract] [Full Text]

				T. Kobayashi, T. Miura, T. Haba, M. Sato, I. Serizawa, H. Nagai, and K. Ishizaka An Essential Role of Mast Cells in the Development of Airway Hyperresponsiveness in a Murine Asthma Model J. Immunol., April 1, 2000; 164(7): 3855 - 3861. [Abstract] [Full Text] [PDF]

				L. Cohn, R. J. Homer, N. Niu, and K. Bottomly T Helper 1 Cells and Interferon {gamma} Regulate Allergic Airway Inflammation and Mucus Production J. Exp. Med., November 1, 1999; 190(9): 1309 - 1318. [Abstract] [Full Text] [PDF]

				Q. Sun, K. Jones, B. McClure, B. Cambareri, B. Zacharakis, P.O. Iversen, F. Stomski, J.M. Woodcock, C.J. Bagley, R. D'Andrea, et al. Simultaneous Antagonism of Interleukin-5, Granulocyte-Macrophage Colony-Stimulating Factor, and Interleukin-3 Stimulation of Human Eosinophils by Targetting the Common Cytokine Binding Site of Their Receptors Blood, September 15, 1999; 94(6): 1943 - 1951. [Abstract] [Full Text] [PDF]

				L. J. WOOD, R. SEHMI, G. M. GAUVREAU, R. M. WATSON, R. FOLEY, J. A. DENBURG, and P. M. O'BYRNE An Inhaled Corticosteroid, Budesonide, Reduces Baseline but Not Allergen-induced Increases in Bone Marrow Inflammatory Cell Progenitors in Asthmatic Subjects Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1457 - 1463. [Abstract] [Full Text] [PDF]

				J. T. Wise, T. J. Baginski, and J. L. Mobley An Adoptive Transfer Model of Allergic Lung Inflammation in Mice Is Mediated by CD4+CD62LlowCD25+ T Cells J. Immunol., May 1, 1999; 162(9): 5592 - 5600. [Abstract] [Full Text] [PDF]

				S. P. Umland, H. Shah, J. P. Jakway, J. Shortall, S. Razac, C. G. Garlisi, A. Falcone, T. T. Kung, D. Stelts, V. Hegde, et al. Effects of Cyclosporin A and Dinactin on T-Cell Proliferation, Interleukin-5 Production, and Murine Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., March 1, 1999; 20(3): 481 - 492. [Abstract] [Full Text]

				C. G. Garlisi, T. T. Kung, P. Wang, M. Minnicozzi, S. P. Umland, R. W. Chapman, D. Stelts, Y. Crawley, A. Falcone, J. G. Myers, et al. Effects of Chronic Anti-Interleukin-5 Monoclonal Antibody Treatment in a Murine Model of Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 1999; 20(2): 248 - 255. [Abstract] [Full Text]

				M. MATHUR, K. HERRMANN, X. LI, Y. QIN, J. WEINSTOCK, D. ELLIOTT, J. MONAHAN, and P. PADRID TRFK-5 Reverses Established Airway Eosinophilia But Not Established Hyperresponsiveness in a Murine Model of Chronic Asthma Am. J. Respir. Crit. Care Med., February 1, 1999; 159(2): 580 - 587. [Abstract] [Full Text]

				R. T. Palframan, P. D. Collins, N. J. Severs, S. Rothery, T. J. Williams, and S. M. Rankin Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase J. Exp. Med., November 2, 1998; 188(9): 1621 - 1632. [Abstract] [Full Text] [PDF]

				E. M. MINSHALL, R. SCHLEIMER, L. CAMERON, M. MINNICOZZI, R. W. EGAN, J.-C. GUTIERREZ-RAMOS, D. H. EIDELMAN, and Q. HAMID Interleukin-5 Expression in the Bone Marrow of Sensitized Balb/c Mice after Allergen Challenge Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 951 - 957. [Abstract] [Full Text] [PDF]

				A. Keane-Myers, M. Wysocka, G. Trinchieri, and M. Wills-Karp Resistance to Antigen-Induced Airway Hyperresponsiveness Requires Endogenous Production of IL-12 J. Immunol., July 15, 1998; 161(2): 919 - 926. [Abstract] [Full Text] [PDF]

				S. P. Umland, S. Razac, H. Shah, D. Kyle Nahrebne, R. W. Egan, and M. Motasim Billah Interleukin-5 mRNA Stability in Human T Cells Is Regulated Differently than Interleukin-2, Interleukin-3, Interleukin-4, Granulocyte/Macrophage Colony-stimulating Factor, and Interferon-gamma Am. J. Respir. Cell Mol. Biol., May 1, 1998; 18(5): 631 - 642. [Abstract] [Full Text]

				D. Stelts, R. W. Egan, A. Falcone, C. G. Garlisi, G. J. Gleich, W. Kreutner, T. T. Kung, D. K. Nahrebne, R. W. Chapman, and M. Minnicozzi Eosinophils Retain Their Granule Major Basic Protein in a Murine Model of Allergic Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., April 1, 1998; 18(4): 463 - 470. [Abstract] [Full Text]

				R. T. Palframan, P. D. Collins, T. J. Williams, and S. M. Rankin Eotaxin Induces a Rapid Release of Eosinophils and Their Progenitors From the Bone Marrow Blood, April 1, 1998; 91(7): 2240 - 2248. [Abstract] [Full Text] [PDF]

				J. E. Chin, G. E. Winterrowd, C. A. Hatfield, J. R. Brashler, R. L. Griffin, S. L. Vonderfecht, K. P. Kolbasa, S. F. Fidler, K. L. Shull, R. F. Krzesicki, et al. Involvement of Intercellular Adhesion Molecule-1 in the Antigen-induced Infiltration of Eosinophils and Lymphocytes into the Airways in a Murine Model of Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 1998; 18(2): 158 - 167. [Abstract] [Full Text]

				X.-M. Li, B. H. Schofield, Q.-F. Wang, K.-H. Kim, and S.-K. Huang Induction of Pulmonary Allergic Responses by Antigen-Specific Th2 Cells J. Immunol., February 1, 1998; 160(3): 1378 - 1384. [Abstract] [Full Text] [PDF]

				C. G. Garlisi, A. Falcone, J. A. Hey, T. M. Paster, X. Fernandez, C. A. Rizzo, M. Minnicozzi, H. Jones, M. Motasim Billah, R. W. Egan, et al. Airway Eosinophils, T Cells, Th2-Type Cytokine mRNA, and Hyperreactivity in Response to Aerosol Challenge of Allergic Mice with Previously Established Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., November 1, 1997; 17(5): 642 - 651. [Abstract] [Full Text]

				L. S. Feder, D. Stelts, R. W. Chapman, D. Manfra, Y. Crawley, H. Jones, M. Minnicozzi, X. Fernandez, T. Paster, R. W. Egan, et al. Role of Nitric Oxide on Eosinophilic Lung Inflammation in Allergic Mice Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 436 - 442. [Abstract] [Full Text]

				G. T. De Sanctis, W. W. Wolyniec, F. H. Y. Green, S. Qin, A. Jiao, P. W. Finn, T. Noonan, A. A. Joetham, E. Gelfand, C. M. Doerschuk, et al. Reduction of allergic airway responses in P-selectin-deficient mice J Appl Physiol, September 1, 1997; 83(3): 681 - 687. [Abstract] [Full Text] [PDF]

				M. McKinnon, K. Page, I. J. Uings, M. Banks, D. Fattah, A. E.I. Proudfoot, P. Graber, C. Arod, R. Fish, T. N.C. Wells, et al. An Interleukin 5 Mutant Distinguishes between Two Functional Responses in Human Eosinophils J. Exp. Med., July 7, 1997; 186(1): 121 - 129. [Abstract] [Full Text] [PDF]

				J. P. Justice, J. Crosby, M. T. Borchers, A. Tomkinson, J. J. Lee, and N. A. Lee CD4+ T cell-dependent airway mucus production occurs in response to IL-5 expression in lung Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L1066 - L1074. [Abstract] [Full Text] [PDF]