M Humbert, S Ying, C Corrigan, G Menz, J Barkans, R Pfister, Q Meng, J Van Damme, G Opdenakker, SR Durham and AB Kay
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.

Intrinsic (nonatopic) asthma is considered to be a distinct pathogenetic variant of asthma since, unlike extrinsic (atopic) asthma, patients are skin-prick test negative to common aeroallergens and have total serum immunoglobulin E concentrations within the normal range. However both atopic and nonatopic asthma are characterized by chronic inflammation of the bronchial mucosa in which eosinophils are prominent and are believed to be associated with local tissue damage. Therefore, specific eosinophil chemoattractants acting in concert with factors which prolong eosinophil survival may at least partly account for selective eosinophil recruitment to the asthmatic bronchial mucosa. The CC chemokines RANTES and monocyte chemotactic protein 3 (MCP-3) are potent eosinophil chemotactic factors, while the cytokines interleukin (IL)-5, granulocyte macrophage-colony-stimulating factor (GM-CSF), and IL-3 prolong eosinophil survival. We have tested the hypothesis that elevated numbers of cells expressing mRNA for RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 are present in bronchial biopsies from atopic and nonatopic asthmatics compared with atopic and nonatopic nonasthmatic controls. The technique of in situ hybridization using 35S- labeled riboprobes was employed to detect mRNA+ bronchial mucosal cells. Compared with controls we observed significant increases in the numbers of cells expressing RANTES and MCP-3, as well as IL-5, GM-CSF, and IL-3 (all P values < 0.001) in atopic and nonatopic asthmatics. These observations support the view that atopic and nonatopic asthma are associated with combined bronchial mucosal expression of CC chemokines (RANTES and MCP-3), together with eosinophil-active cytokines (IL-5, GM-CSF, and IL-3). These cytokines might contribute to the bronchial mucosal accumulation of activated eosinophils in both atopic and nonatopic variants of asthma.

This article has been cited by other articles:

				P. K. Jeffery Remodeling and Inflammation of Bronchi in Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2004; 1(3): 176 - 183. [Abstract] [Full Text] [PDF]

				R H Green, C E Brightling, G Woltmann, D Parker, A J Wardlaw, and I D Pavord Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids Thorax, October 1, 2002; 57(10): 875 - 879. [Abstract] [Full Text] [PDF]

				N. Hizawa, E. Yamaguchi, S. Konno, Y. Tanino, E. Jinushi, and M. Nishimura A Functional Polymorphism in the RANTES Gene Promoter Is Associated with the Development of Late-Onset Asthma Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 686 - 690. [Abstract] [Full Text] [PDF]

				X.-Z. Shang, B.-C. Chiu, V. Stolberg, N. W. Lukacs, S. L. Kunkel, H. S. Murphy, and S. W. Chensue Eosinophil Recruitment in Type-2 Hypersensitivity Pulmonary Granulomas : Source and Contribution of Monocyte Chemotactic Protein-3 (CCL7) Am. J. Pathol., July 1, 2002; 161(1): 257 - 266. [Abstract] [Full Text] [PDF]

				R. Crameri and K. Blaser Allergy and immunity to fungal infections and colonization Eur. Respir. J., January 1, 2002; 19(1): 151 - 157. [Abstract] [Full Text] [PDF]

				M. J. Holtzman, J. D. Morton, L. P. Shornick, J. W. Tyner, M. P. O'Sullivan, A. Antao, M. Lo, M. Castro, and M. J. Walter Immunity, Inflammation, and Remodeling in the Airway Epithelial Barrier: Epithelial-Viral-Allergic Paradigm Physiol Rev, January 1, 2002; 82(1): 19 - 46. [Abstract] [Full Text] [PDF]

				E L J van Rensen, R G Stirling, J Scheerens, K Staples, P J Sterk, P J Barnes, and K F Chung Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma Thorax, December 1, 2001; 56(12): 935 - 940. [Abstract] [Full Text] [PDF]

				A. M. Abu El-Asrar, I. Van Aelst, S. Al-Mansouri, L. Missotten, G. Opdenakker, and K. Geboes Gelatinase B in Vernal Keratoconjunctivitis Arch Ophthalmol, October 1, 2001; 119(10): 1505 - 1511. [Abstract] [Full Text] [PDF]

				K. Miura, S. S. Saini, G. Gauvreau, and D. W. MacGlashan Jr Differences in Functional Consequences and Signal Transduction Induced by IL-3, IL-5, and Nerve Growth Factor in Human Basophils J. Immunol., August 15, 2001; 167(4): 2282 - 2291. [Abstract] [Full Text] [PDF]

				K.F. Chung Cytokines in chronic obstructive pulmonary disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s. [Abstract] [Full Text] [PDF]

				J. ZHU, Y. S. QIU, S. MAJUMDAR, E. GAMBLE, D. MATIN, G. TURATO, L. M. FABBRI, N. BARNES, M. SAETTA, and P. K. JEFFERY Exacerbations of Bronchitis . Bronchial Eosinophilia and Gene Expression for Interleukin-4, Interleukin-5, and Eosinophil Chemoattractants Am. J. Respir. Crit. Care Med., July 1, 2001; 164(1): 109 - 116. [Abstract] [Full Text] [PDF]

				A. M A. El-Asrar, S. Struyf, S. A Al-Kharashi, L. Missotten, J. Van Damme, and K. Geboes Chemokines in the limbal form of vernal keratoconjunctivitis Br. J. Ophthalmol., December 1, 2000; 84(12): 1360 - 1366. [Abstract] [Full Text]

				R. Bheekha-Escura, D. W. MacGlashan Jr, J. M. Langdon, and S. M. MacDonald Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10 Blood, September 15, 2000; 96(6): 2191 - 2198. [Abstract] [Full Text] [PDF]

				I. TILLIE-LEBLOND, H. HAMMAD, S. DESURMONT, J. PUGIN, B. WALLAERT, A.-B. TONNEL, and P. GOSSET CC Chemokines and Interleukin-5 in Bronchial Lavage Fluid from Patients with Status Asthmaticus . Potential Implication in Eosinophil Recruitment Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 586 - 592. [Abstract] [Full Text] [PDF]

				B. LAMKHIOUED, E. A. GARCIA-ZEPEDA, S. ABI-YOUNES, H. NAKAMURA, S. JEDRZKIEWICZ, L. WAGNER, P. M. RENZI, Z. ALLAKHVERDI, C. LILLY, Q. HAMID, et al. Monocyte Chemoattractant Protein (MCP)-4 Expression in the Airways of Patients with Asthma . Induction in Epithelial Cells and Mononuclear Cells by Proinflammatory Cytokines Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 723 - 732. [Abstract] [Full Text] [PDF]

				M. Bergmann, P. J. Barnes, and R. Newton Molecular Regulation of Granulocyte Macrophage Colony-Stimulating Factor in Human Lung Epithelial Cells by Interleukin (IL)-1beta , IL-4, and IL-13 Involves Both Transcriptional and Post-Transcriptional Mechanisms Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 582 - 589. [Abstract] [Full Text]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				M. E. Bates, V. L. Green, and P. J. Bertics ERK1 and ERK2 Activation by Chemotactic Factors in Human Eosinophils Is Interleukin 5-dependent and Contributes to Leukotriene C4 Biosynthesis J. Biol. Chem., April 6, 2000; 275(15): 10968 - 10975. [Abstract] [Full Text] [PDF]

				S. Shahabuddin, P. Ponath, and R. P. Schleimer Migration of Eosinophils Across Endothelial Cell Monolayers: Interactions Among IL-5, Endothelial-Activating Cytokines, and C-C Chemokines J. Immunol., April 1, 2000; 164(7): 3847 - 3854. [Abstract] [Full Text] [PDF]

				K. Miura and D. W. MacGlashan Jr. Dual Phase Priming by IL-3 for Leukotriene C4 Generation in Human Basophils: Difference in Characteristics Between Acute and Late Priming Effects J. Immunol., March 15, 2000; 164(6): 3026 - 3034. [Abstract] [Full Text] [PDF]

				C. E. Donovan, D. A. Mark, H. Z. He, H.-C. Liou, L. Kobzik, Y. Wang, G. T. De Sanctis, D. L. Perkins, and P. W. Finn NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation J. Immunol., December 15, 1999; 163(12): 6827 - 6833. [Abstract] [Full Text] [PDF]

				Z. H. Jaffar, L. Stanciu, A. Pandit, J. Lordan, S. T. Holgate, and K. Roberts Essential Role for Both CD80 and CD86 Costimulation, But Not CD40 Interactions, in Allergen-Induced Th2 Cytokine Production from Asthmatic Bronchial Tissue: Role for {alpha}{beta}, But Not {gamma}{delta}, T Cells J. Immunol., December 1, 1999; 163(11): 6283 - 6291. [Abstract] [Full Text] [PDF]

				S. Ying, Q. Meng, K. Zeibecoglou, D. S. Robinson, A. Macfarlane, M. Humbert, and A. B. Kay Eosinophil Chemotactic Chemokines (Eotaxin, Eotaxin-2, RANTES, Monocyte Chemoattractant Protein-3 (MCP-3), and MCP-4), and C-C Chemokine Receptor 3 Expression in Bronchial Biopsies from Atopic and Nonatopic (Intrinsic) Asthmatics J. Immunol., December 1, 1999; 163(11): 6321 - 6329. [Abstract] [Full Text] [PDF]

				C. Stellato, S. Matsukura, A. Fal, J. White, L. A. Beck, D. Proud, and R. P. Schleimer Differential Regulation of Epithelial-Derived C-C Chemokine Expression by IL-4 and the Glucocorticoid Budesonide J. Immunol., November 15, 1999; 163(10): 5624 - 5632. [Abstract] [Full Text] [PDF]

				J. L. Pype, L. J. Dupont, P. Menten, E. Van Coillie, G. Opdenakker, J. Van Damme, K. Fan Chung, M. G. Demedts, and G. M. Verleden Expression of Monocyte Chemotactic Protein (MCP)-1, MCP-2, and MCP-3 by Human Airway Smooth-Muscle Cells . Modulation by Corticosteroids and T-Helper 2 Cytokines Am. J. Respir. Cell Mol. Biol., October 1, 1999; 21(4): 528 - 536. [Abstract] [Full Text]

				S. Ying, D. S. Robinson, Q. Meng, L. T. Barata, A. R. McEuen, M. G. Buckley, A. F. Walls, P. W. Askenase, and A. B. Kay C-C Chemokines in Allergen-Induced Late-Phase Cutaneous Responses in Atopic Subjects: Association of Eotaxin with Early 6-Hour Eosinophils, and of Eotaxin-2 and Monocyte Chemoattractant Protein-4 with the Later 24-Hour Tissue Eosinophilia, and Relationship to Basophils and Other C-C Chemokines (Monocyte Chemoattractant Protein-3 and RANTES) J. Immunol., October 1, 1999; 163(7): 3976 - 3984. [Abstract] [Full Text] [PDF]

				K F Chung and P J Barnes Cytokines in asthma Thorax, September 1, 1999; 54(9): 825 - 857. [Full Text]

				G. Devouassoux, D. D. Metcalfe, and C. Prussin Eotaxin Potentiates Antigen-Dependent Basophil IL-4 Production J. Immunol., September 1, 1999; 163(5): 2877 - 2882. [Abstract] [Full Text] [PDF]

				C. A. McNulty, F. A. Symon, and A. J. Wardlaw Characterization of the Integrin and Activation Steps Mediating Human Eosinophil and Neutrophil Adhesion to Chronically Inflamed Airway Endothelium Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1251 - 1259. [Abstract] [Full Text]

				J Wedemeyer, A Lorentz, M Goke, P N Meier, P Flemming, C A Dahinden, M P Manns, and S C Bischoff Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa Gut, May 1, 1999; 44(5): 629 - 635. [Abstract] [Full Text] [PDF]

				S. Struyf, P. Proost, D. Schols, E. De Clercq, G. Opdenakker, J.-P. Lenaerts, M. Detheux, M. Parmentier, I. De Meester, S. Scharpe, et al. CD26/Dipeptidyl-Peptidase IV Down-Regulates the Eosinophil Chemotactic Potency, But Not the Anti-HIV Activity of Human Eotaxin by Affecting Its Interaction with CC Chemokine Receptor 3 J. Immunol., April 15, 1999; 162(8): 4903 - 4909. [Abstract] [Full Text] [PDF]

				L. M. Teran, M. Mochizuki, J. Bartels, E. L. Valencia, T. Nakajima, K. Hirai, and J.-M. Schröder Th1- and Th2-Type Cytokines Regulate the Expression and Production of Eotaxin and RANTES by Human Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 777 - 786. [Abstract] [Full Text]

				A. Sauty, M. Dziejman, R. A. Taha, A. S. Iarossi, K. Neote, E. A. Garcia-Zepeda, Q. Hamid, and A. D. Luster The T Cell-Specific CXC Chemokines IP-10, Mig, and I-TAC Are Expressed by Activated Human Bronchial Epithelial Cells J. Immunol., March 15, 1999; 162(6): 3549 - 3558. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				K. J. HALEY, M. E. SUNDAY, B. R. WIGGS, H. P. KOZAKEWICH, J. J. REILLY, S. J. MENTZER, D. J. SUGARBAKER, C. M. DOERSCHUK, and J. M. DRAZEN Inflammatory Cell Distribution within and along Asthmatic Airways Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 565 - 572. [Abstract] [Full Text] [PDF]

				M. Taguchi, D. Sampath, T. Koga, M. Castro, D. C. Look, S. Nakajima, and M. J. Holtzman Patterns for RANTES Secretion and Intercellular Adhesion Molecule 1 Expression Mediate Transepithelial T Cell Traffic Based on Analyses In Vitro and In Vivo J. Exp. Med., June 15, 1998; 187(12): 1927 - 1940. [Abstract] [Full Text] [PDF]

				A. D. Luster Chemokines -- Chemotactic Cytokines That Mediate Inflammation N. Engl. J. Med., February 12, 1998; 338(7): 436 - 445. [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]

				M. HUMBERT, C. J. CORRIGAN, P. KIMMITT, S. J. TILL, A. BARRY KAY, and S. R. DURHAM Relationship between IL-4 and IL-5 mRNA Expression and Disease Severity in Atopic Asthma Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 704 - 708. [Abstract] [Full Text] [PDF]