| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, London, United Kingdom;
Children’s Hospital, Harvard Medical School, Boston, MA 02115; and
LeukoSite Inc., Cambridge, MA 02142
Certain C-C chemokines, signaling via the eotaxin receptor C-C chemokine receptor-3 (CCR3), are thought to be central mediators of eosinophil accumulation in allergic inflammation. To investigate the role of CCR3 in vivo, we cloned the guinea pig eotaxin receptor (guinea pig CCR3) from a genomic DNA library. We isolated a single-exon open reading frame coding for a 358-amino acid chemokine receptor protein with 67 and 69% homology to human and murine CCR3, respectively. When expressed in stable transfectants, this receptor bound 125I-labeled guinea pig eotaxin, 125I-labeled human monocyte chemotactic protein-3, and 125I-labeled human RANTES. In chemotaxis assays, guinea pig CCR3 transfectants responded only to guinea pig eotaxin, with a maximal effect at 100 nM. mAbs were raised that bound selectively to both guinea pig CCR3 transfectants and guinea pig eosinophils. One of these mAbs, 2A8, blocked both ligand binding to transfectants and their chemotaxis in response to eotaxin. The Ab also inhibited chemotaxis and the elevation of cytosolic calcium in guinea pig eosinophils in response to eotaxin. F(ab')2 fragments of 2A8 were prepared that retained the ability to inhibit eosinophil calcium responses to eotaxin. Pretreatment of 111In-labeled eosinophils in vitro with F(ab')2 2A8 selectively inhibited their accumulation in response to eotaxin in vivo. These data demonstrate that functional blockade of eosinophil chemokine receptors can be achieved in vivo and provide further support for the development of novel anti-inflammatory drugs targeting eosinophil recruitment through chemokine receptor antagonism.
This article has been cited by other articles:
|
|
 |
|
  A.H. Nissim Ben Efraim and F. Levi-Schaffer Review: Tissue remodeling and angiogenesis in asthma: the role of the eosinophil Therapeutic Advances in Respiratory Disease, June 1, 2008; 2(3): 163 - 171. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Meiser, A. Mueller, E. L. Wise, E. M. McDonagh, S. J. Petit, N. Saran, P. C. Clark, T. J. Williams, and J. E. Pease The Chemokine Receptor CXCR3 Is Degraded following Internalization and Is Replenished at the Cell Surface by De Novo Synthesis of Receptor J. Immunol., May 15, 2008; 180(10): 6713 - 6724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Rosenkilde, T. Benned-Jensen, H. Andersen, P. J. Holst, T. N. Kledal, H. R. Luttichau, J. K. Larsen, J. P. Christensen, and T. W. Schwartz Molecular Pharmacological Phenotyping of EBI2: AN ORPHAN SEVEN-TRANSMEMBRANE RECEPTOR WITH CONSTITUTIVE ACTIVITY J. Biol. Chem., May 12, 2006; 281(19): 13199 - 13208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Morokata, K. Suzuki, Y. Masunaga, K. Taguchi, K. Morihira, I. Sato, M. Fujii, S. Takizawa, Y. Torii, N. Yamamoto, et al. A Novel, Selective, and Orally Available Antagonist for CC Chemokine Receptor 3 J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 244 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Fritz, C. Kerr, L. Tong, D. Smyth, and C. D. Richards Oncostatin-M Up-Regulates VCAM-1 and Synergizes with IL-4 in Eotaxin Expression: Involvement of STAT6 J. Immunol., April 1, 2006; 176(7): 4352 - 4360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Lukacs, A. L. Miller, and C. M. Hogaboam Chemokine Receptors in Asthma: Searching for the Correct Immune Targets J. Immunol., July 1, 2003; 171(1): 11 - 15. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Phillips, V. E. L. Stubbs, M. R. Henson, T. J. Williams, J. E. Pease, and I. Sabroe Variations in Eosinophil Chemokine Responses: An Investigation of CCR1 and CCR3 Function, Expression in Atopy, and Identification of a Functional CCR1 Promoter J. Immunol., June 15, 2003; 170(12): 6190 - 6201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, M. P. Soares, Y. Guan, S. Matheravidathu, R. Wnek, K. E. Johnson, A. Meisher, S. A. Iliff, J. S. Mudgett, M. S. Springer, et al. Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies J. Biol. Chem., September 6, 2002; 277(37): 33799 - 33810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Bryan, P. J. Jose, J. R. Topping, R. Wilhelm, C. Soderberg, D. Kertesz, P. J. Barnes, T. J. Williams, T. T. Hansel, and I. Sabroe Responses of Leukocytes to Chemokines in Whole Blood and Their Antagonism by Novel CC-Chemokine Receptor 3 Antagonists Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1602 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Jopling, I. Sabroe, D. P. Andrew, T. J. Mitchell, Y. Li, M. R. Hodge, T. J. Williams, and J. E. Pease The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody J. Biol. Chem., February 22, 2002; 277(9): 6864 - 6873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Penido, H. C. Castro-Faria-Neto, A. Vieira-de-Abreu, R. T. Figueiredo, A. Pelled, M. A. Martins, P. J. Jose, T. J. Williams, and P. T. Bozza LPS Induces Eosinophil Migration via CCR3 Signaling Through a Mechanism Independent of RANTES and Eotaxin Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 707 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Martinelli, I. Sabroe, G. LaRosa, T. J. Williams, and J. E. Pease The CC Chemokine Eotaxin (CCL11) Is a Partial Agonist of CC Chemokine Receptor 2b J. Biol. Chem., November 9, 2001; 276(46): 42957 - 42964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Qiu, K. A. Frait, F. Reich, E. Komuniecki, and S. W. Chensue Chemokine Expression Dynamics in Mycobacterial (Type-1) and Schistosomal (Type-2) Antigen-Elicited Pulmonary Granuloma Formation Am. J. Pathol., April 1, 2001; 158(4): 1503 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. B. Nibbs, E. Kriehuber, P. D. Ponath, D. Parent, S. Qin, J. D. M. Campbell, A. Henderson, D. Kerjaschki, D. Maurer, G. J. Graham, et al. The {beta}-Chemokine Receptor D6 Is Expressed by Lymphatic Endothelium and a Subset of Vascular Tumors Am. J. Pathol., March 1, 2001; 158(3): 867 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stellato, M. E. Brummet, J. R. Plitt, S. Shahabuddin, F. M. Baroody, M. C. Liu, P. D. Ponath, and L. A. Beck Cutting Edge: Expression of the C-C Chemokine Receptor CCR3 in Human Airway Epithelial Cells J. Immunol., February 1, 2001; 166(3): 1457 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Heinemann, A. Hartnell, V. E. L. Stubbs, K. Murakami, D. Soler, G. LaRosa, P. W. Askenase, T. J. Williams, and I. Sabroe Basophil Responses to Chemokines Are Regulated by Both Sequential and Cooperative Receptor Signaling J. Immunol., December 15, 2000; 165(12): 7224 - 7233. [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]
|
|
|
|
|
|
N. Matsushita, N. Nishi, M. Seki, R. Matsumoto, I. Kuwabara, F.-T. Liu, Y. Hata, T. Nakamura, and M. Hirashima Requirement of Divalent Galactoside-binding Activity of Ecalectin/Galectin-9 for Eosinophil Chemoattraction J. Biol. Chem., March 17, 2000; 275(12): 8355 - 8360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sabroe, A. Hartnell, L. A. Jopling, S. Bel, P. D. Ponath, J. E. Pease, P. D. Collins, and T. J. Williams Differential Regulation of Eosinophil Chemokine Signaling Via CCR3 and Non-CCR3 Pathways J. Immunol., March 1, 1999; 162(5): 2946 - 2955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sabroe, M. J. Peck, B. J. Van Keulen, A. Jorritsma, G. Simmons, P. R. Clapham, T. J. Williams, and J. E. Pease A Small Molecule Antagonist of Chemokine Receptors CCR1 and CCR3. POTENT INHIBITION OF EOSINOPHIL FUNCTION AND CCR3-MEDIATED HIV-1 ENTRY J. Biol. Chem., August 18, 2000; 275(34): 25985 - 25992. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
