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*
Departments of Pathology and
Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94309
Bronchial eosinophil and mononuclear cell infiltrates are a
hallmark of the asthmatic lung and are associated with the induction of
reversible airway hyperreactivity. In these studies, we have found that
monocyte chemotactic protein-1 (MCP-1), a CC (ß) chemokine, mediates
airway hyperreactivity in normal and allergic mice. Using a murine
model of cockroach Ag-induced allergic airway inflammation, we have
demonstrated that anti-MCP-1 Abs inhibit changes in airway
resistance and attenuate histamine release into the bronchoalveolar
lavage, suggesting a role for MCP-1 in mast cell degranulation. In
normal mice, instillation of MCP-1 induced prolonged airway
hyperreactivity and histamine release. In addition, MCP-1 directly
induced pulmonary mast cell degranulation in vitro. These latter
effects would appear to be selective because no changes were observed
when macrophage-inflammatory protein-1
, eotaxin, or MCP-3 were
instilled into the airways of normal mice or when mast cells were
treated in vitro. Airway hyperreactivity was mediated by MCP-1 through
CCR2 because allergen-induced as well as direct MCP-1 instilled-induced
changes in airway hyperreactivity were significantly attenuated in CCR2
-/- mice. The neutralization of MCP-1 in allergic animals
and instillation of MCP-1 in normal animals was related to leukotriene
C4 levels in the bronchoalveolar lavage and was directly
induced in pulmonary mast cells by MCP-1. Thus, these data identify
MCP-1 and CCR2 as potentially important therapeutic targets for the
treatment of hyperreactive airway disease.
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K. Raman, M. H. Kaplan, C. M. Hogaboam, A. Berlin, and N. W. Lukacs STAT4 Signal Pathways Regulate Inflammation and Airway Physiology Changes in Allergic Airway Inflammation Locally Via Alteration of Chemokines J. Immunol., April 1, 2003; 170(7): 3859 - 3865. [Abstract] [Full Text] [PDF]
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B. B. Vargaftig and M. Singer Leukotrienes, IL-13, and chemokines cooperate to induce BHR and mucus in allergic mouse lungs Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L260 - L269. [Abstract] [Full Text] [PDF]
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N. W. Lukacs, A. John, A. Berlin, D. C. Bullard, R. Knibbs, and L. M. Stoolman E- and P-Selectins Are Essential for the Development of Cockroach Allergen-Induced Airway Responses J. Immunol., August 15, 2002; 169(4): 2120 - 2125. [Abstract] [Full Text] [PDF]
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T. R. Traynor, A. C. Herring, M. E. Dorf, W. A. Kuziel, G. B. Toews, and G. B. Huffnagle Differential Roles of CC Chemokine Ligand 2/Monocyte Chemotactic Protein-1 and CCR2 in the Development of T1 Immunity J. Immunol., May 1, 2002; 168(9): 4659 - 4666. [Abstract] [Full Text] [PDF]
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D. S. Southam, M. Dolovich, P. M. O'Byrne, and M. D. Inman Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L833 - L839. [Abstract] [Full Text] [PDF]
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N. W. Lukacs, A. Berlin, D. Schols, R. T. Skerlj, and G. J. Bridger AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity Am. J. Pathol., April 1, 2002; 160(4): 1353 - 1360. [Abstract] [Full Text] [PDF]
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Z. Zhu, B. Ma, T. Zheng, R. J. Homer, C. G. Lee, I. F. Charo, P. Noble, and J. A. Elias IL-13-Induced Chemokine Responses in the Lung: Role of CCR2 in the Pathogenesis of IL-13-Induced Inflammation and Remodeling J. Immunol., March 15, 2002; 168(6): 2953 - 2962. [Abstract] [Full Text] [PDF]
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J. H. Lee, N. Kaminski, G. Dolganov, G. Grunig, L. Koth, C. Solomon, D. J. Erle, and D. Sheppard Interleukin-13 Induces Dramatically Different Transcriptional Programs in Three Human Airway Cell Types Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 474 - 485. [Abstract] [Full Text] [PDF]
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J. Ahamed, B. Haribabu, and H. Ali Cutting Edge: Differential Regulation of Chemoattractant Receptor-Induced Degranulation and Chemokine Production by Receptor Phosphorylation J. Immunol., October 1, 2001; 167(7): 3559 - 3563. [Abstract] [Full Text] [PDF]
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N. W. Lukacs, K. K. Tekkanat, A. Berlin, C. M. Hogaboam, A. Miller, H. Evanoff, P. Lincoln, and H. Maassab Respiratory Syncytial Virus Predisposes Mice to Augmented Allergic Airway Responses Via IL-13-Mediated Mechanisms J. Immunol., July 15, 2001; 167(2): 1060 - 1065. [Abstract] [Full Text] [PDF]
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 P.J. Barnes Cytokine modulators as novel therapies for airway disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s. [Abstract] [Full Text] [PDF]
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S. H. P. Oliveira, C. M. Hogaboam, A. Berlin, and N. W. Lukacs SCF-induced airway hyperreactivity is dependent on leukotriene production Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1242 - L1249. [Abstract] [Full Text] [PDF]
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Y. Kim, S.-s. J. Sung, W. A. Kuziel, S. Feldman, S. M. Fu, and C. E. Rose Jr Enhanced Airway Th2 Response After Allergen Challenge in Mice Deficient in CC Chemokine Receptor-2 (CCR2) J. Immunol., April 15, 2001; 166(8): 5183 - 5192. [Abstract] [Full Text] [PDF]
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M. Mack, J. Cihak, C. Simonis, B. Luckow, A. E. I. Proudfoot, H. Bruhl, M. Frink, H.-J. Anders, V. Vielhauer, J. Pfirstinger, et al. Expression and Characterization of the Chemokine Receptors CCR2 and CCR5 in Mice J. Immunol., April 1, 2001; 166(7): 4697 - 4704. [Abstract] [Full Text] [PDF]
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S. W. Chensue, N. W. Lukacs, T.-Y. Yang, X. Shang, K. A. Frait, S. L. Kunkel, T. Kung, M. T. Wiekowski, J. A. Hedrick, D. N. Cook, et al. Aberrant in Vivo T Helper Type 2 Cell Response and Impaired Eosinophil Recruitment in Cc Chemokine Receptor 8 Knockout Mice J. Exp. Med., March 5, 2001; 193(5): 573 - 584. [Abstract] [Full Text] [PDF]
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N. W. Lukacs, M. M. Glovsky, and P. A. Ward Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L512 - L518. [Abstract] [Full Text] [PDF]
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K. K. Tekkanat, H. F. Maassab, D. S. Cho, J. J. Lai, A. John, A. Berlin, M. H. Kaplan, and N. W. Lukacs IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent J. Immunol., March 1, 2001; 166(5): 3542 - 3548. [Abstract] [Full Text] [PDF]
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K. Blease, B. Mehrad, N. W. Lukacs, S. L. Kunkel, T. J. Standiford, and C. M. Hogaboam Antifungal and Airway Remodeling Roles for Murine Monocyte Chemoattractant Protein-1/CCL2 During Pulmonary Exposure to Asperigillus fumigatus Conidia J. Immunol., February 1, 2001; 166(3): 1832 - 1842. [Abstract] [Full Text] [PDF]
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J. A. MacLean, G. T. De Sanctis, K. G. Ackerman, J. M. Drazen, A. Sauty, E. DeHaan, F. H. Y. Green, I. F. Charo, and A. D. Luster CC Chemokine Receptor-2 Is Not Essential for the Development of Antigen-Induced Pulmonary Eosinophilia and Airway Hyperresponsiveness J. Immunol., December 1, 2000; 165(11): 6568 - 6575. [Abstract] [Full Text] [PDF]
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B. T. Fife, G. B. Huffnagle, W. A. Kuziel, and W. J. Karpus Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis J. Exp. Med., September 18, 2000; 192(6): 899 - 906. [Abstract] [Full Text] [PDF]
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K. Dabbagh, Y. Xiao, C. Smith, P. Stepick-Biek, S. G. Kim, W. J. E. Lamm, D. H. Liggitt, and D. B. Lewis Local Blockade of Allergic Airway Hyperreactivity and Inflammation by the Poxvirus-Derived Pan-CC-Chemokine Inhibitor vCCI J. Immunol., September 15, 2000; 165(6): 3418 - 3422. [Abstract] [Full Text] [PDF]
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 P. M. Murphy, M. Baggiolini, I. F. Charo, C. A. Hebert, R. Horuk, K. Matsushima, L. H. Miller, J. J. Oppenheim, and C. A. Power International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors Pharmacol. Rev., March 1, 2000; 52(1): 145 - 176. [Abstract] [Full Text] [PDF]
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A. Matsukawa, C. M. Hogaboam, N. W. Lukacs, P. M. Lincoln, R. M. Strieter, and S. L. Kunkel Endogenous Monocyte Chemoattractant Protein-1 (MCP-1) Protects Mice in a Model of Acute Septic Peritonitis: Cross-Talk Between MCP-1 and Leukotriene B4 J. Immunol., December 1, 1999; 163(11): 6148 - 6154. [Abstract] [Full Text] [PDF]
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 T. Mirzadegan, F. Diehl, B. Ebi, S. Bhakta, I. Polsky, D. McCarley, M. Mulkins, G. S. Weatherhead, J.-M. Lapierre, J. Dankwardt, et al. Identification of the Binding Site for a Novel Class of CCR2b Chemokine Receptor Antagonists. BINDING TO A COMMON CHEMOKINE RECEPTOR MOTIF WITHIN THE HELICAL BUNDLE J. Biol. Chem., August 11, 2000; 275(33): 25562 - 25571. [Abstract] [Full Text] [PDF]
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