| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CUTTING EDGE |
*
Institute of Medical Microbiology and
Department of Transplantation Surgery, Medical School, Hannover, Germany;
Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany; and
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406
Asthma is a major cause of morbidity worldwide with
prevalence and severity still increasing at an alarming pace. Hallmarks
of this disease include early-phase bronchoconstriction with subsequent
eosinophil infiltration, symptoms that may be mimicked in
vivo by the complement-derived C3a anaphylatoxin, following its
interaction with the single-copy C3aR. We analyzed the
pathophysiological role of the C3a anaphylatoxin in a model of
experimental OVA-induced allergic asthma, using an inbred guinea pig
strain phenotypically unresponsive to C3a. Molecular analysis of this
defect revealed a point mutation within the coding region of the C3aR
that creates a stop codon, thereby effectively inactivating gene
function. When challenged by OVA inhalation, sensitized animals of this
strain exhibited a bronchoconstriction decreased by 
30% in
comparison to the corresponding wild-type strain. These data suggest an
important role of C3a in the pathogenesis of asthma and define a novel
target for drug intervention strategies.
This article has been cited by other articles:
|
|
 |
|
  X. Zhang, I. P. Lewkowich, G. Kohl, J. R. Clark, M. Wills-Karp, and J. Kohl A Protective Role for C5a in the Development of Allergic Asthma Associated with Altered Levels of B7-H1 and B7-DC on Plasmacytoid Dendritic Cells J. Immunol., April 15, 2009; 182(8): 5123 - 5130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wills-Karp Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma Proceedings of the ATS, July 1, 2007; 4(3): 247 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dillard, R. A. Wetsel, and S. M. Drouin Complement C3a Regulates Muc5ac Expression by Airway Clara Cells Independently of Th2 Responses Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1250 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Deaton, L. Deaton, E. Jose-Cunilleras, T. L. Vincent, A. W. Baird, K. Dacre, and D. J. Marlin Early onset airway obstruction in response to organic dust in the horse J Appl Physiol, March 1, 2007; 102(3): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Melendi, S. J. Hoffman, R. A. Karron, P. M. Irusta, F. R. Laham, A. Humbles, B. Schofield, C.-H. Pan, R. Rabold, B. Thumar, et al. C5 Modulates Airway Hyperreactivity and Pulmonary Eosinophilia during Enhanced Respiratory Syncytial Virus Disease by Decreasing C3a Receptor Expression J. Virol., January 15, 2007; 81(2): 991 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Mueller-Ortiz, T. J. Hollmann, D. L. Haviland, and R. A. Wetsel Ablation of the complement C3a anaphylatoxin receptor causes enhanced killing of Pseudomonas aeruginosa in a mouse model of pneumonia Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L157 - L165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Taube, J. M. Thurman, K. Takeda, A. Joetham, N. Miyahara, M. C. Carroll, A. Dakhama, P. C. Giclas, V. M. Holers, and E. W. Gelfand Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation PNAS, May 23, 2006; 103(21): 8084 - 8089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Drouin, M. Sinha, G. Sfyroera, J. D. Lambris, and R. A. Wetsel A Protective Role for the Fifth Complement Component (C5) in Allergic Airway Disease Am. J. Respir. Crit. Care Med., April 15, 2006; 173(8): 852 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Lee, T. Rhim, Y.-S. Choi, J.-W. Min, S.-H. Kim, S.-Y. Cho, Y.-K. Paik, and C.-S. Park Complement C3a and C4a Increased in Plasma of Patients with Aspirin-induced Asthma Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schaefer, S. Konrad, J. Thalmann, C. Rheinheimer, K. Johswich, B. Sohns, and A. Klos The Transcription Factors AP-1 and Ets Are Regulators of C3a Receptor Expression J. Biol. Chem., December 23, 2005; 280(51): 42113 - 42123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Martin and B. K. Martin Characterization of the Murine C3a Receptor Enhancer-Promoter: Expression Control by an Activator Protein 1 Sequence and an Ets-Like Site J. Immunol., September 1, 2005; 175(5): 3123 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Baelder, B. Fuchs, W. Bautsch, J. Zwirner, J. Kohl, H. G Hoymann, T. Glaab, V. Erpenbeck, N. Krug, and A. Braun Pharmacological Targeting of Anaphylatoxin Receptors during the Effector Phase of Allergic Asthma Suppresses Airway Hyperresponsiveness and Airway Inflammation J. Immunol., January 15, 2005; 174(2): 783 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Marc, P. Korosec, M. Kosnik, I. Kern, M. Flezar, S. Suskovic, and J. Sorli Complement Factors C3a, C4a, and C5a in Chronic Obstructive Pulmonary Disease and Asthma Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 216 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ahamed, R. T. Venkatesha, E. B. Thangam, and H. Ali C3a Enhances Nerve Growth Factor-Induced NFAT Activation and Chemokine Production in a Human Mast Cell Line, HMC-1 J. Immunol., June 1, 2004; 172(11): 6961 - 6968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Park, C. Taube, A. Joetham, K. Takeda, T. Kodama, A. Dakhama, G. McConville, C. B. Allen, G. Sfyroera, L. D. Shultz, et al. Complement Activation Is Critical to Airway Hyperresponsiveness after Acute Ozone Exposure Am. J. Respir. Crit. Care Med., March 15, 2004; 169(6): 726 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Taube, Y.-H. Rha, K. Takeda, J.-W. Park, A. Joetham, A. Balhorn, A. Dakhama, P. C. Giclas, V. M. Holers, and E. W. Gelfand Inhibition of Complement Activation Decreases Airway Inflammation and Hyperresponsiveness Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1333 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Grant, D. Picarella, T. Burwell, T. Delaney, A. Croci, N. Avitahl, A. A. Humbles, J.-C. Gutierrez-Ramos, M. Briskin, C. Gerard, et al. Essential Role for the C5a Receptor in Regulating the Effector Phase of Synovial Infiltration and Joint Destruction in Experimental Arthritis J. Exp. Med., December 2, 2002; 196(11): 1461 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Drouin, D. B. Corry, T. J. Hollman, J. Kildsgaard, and R. A. Wetsel Absence of the Complement Anaphylatoxin C3a Receptor Suppresses Th2 Effector Functions in a Murine Model of Pulmonary Allergy J. Immunol., November 15, 2002; 169(10): 5926 - 5933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Walters, P. N. Breysse, B. Schofield, and M. Wills-Karp Complement Factor 3 Mediates Particulate Matter-Induced Airway Hyperresponsiveness Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 413 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Venkayya, M. Lam, M. Willkom, G. Grunig, D. B. Corry, and D. J. Erle The Th2 Lymphocyte Products IL-4 and IL-13 Rapidly Induce Airway Hyperresponsiveness Through Direct Effects on Resident Airway Cells Am. J. Respir. Cell Mol. Biol., February 1, 2002; 26(2): 202 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Burke-Gaffney, K. Blease, A. Hartnell, and P. G. Hellewell TNF-{alpha} Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for {alpha}5{beta}1 Integrin J. Immunol., February 1, 2002; 168(3): 1380 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. KRUG, T. TSCHERNIG, V. J. ERPENBECK, J. M. HOHLFELD, and J. KOHL Complement Factors C3a and C5a Are Increased in Bronchoalveolar Lavage Fluid after Segmental Allergen Provocation in Subjects with Asthma Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1841 - 1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Drouin, D. B. Corry, J. Kildsgaard, and R. A. Wetsel Cutting Edge: The Absence of C3 Demonstrates a Role for Complement in Th2 Effector Functions in a Murine Model of Pulmonary Allergy J. Immunol., October 15, 2001; 167(8): 4141 - 4145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abe, K. Shibata, H. Akatsu, N. Shimizu, N. Sakata, T. Katsuragi, and H. Okada Contribution of Anaphylatoxin C5a to Late Airway Responses After Repeated Exposure of Antigen to Allergic Rats J. Immunol., October 15, 2001; 167(8): 4651 - 4660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ames, D. Lee, J. J. Foley, A. J. Jurewicz, M. A. Tornetta, W. Bautsch, B. Settmacher, A. Klos, K. F. Erhard, R. D. Cousins, et al. Identification of a Selective Nonpeptide Antagonist of the Anaphylatoxin C3a Receptor That Demonstrates Antiinflammatory Activity in Animal Models J. Immunol., May 15, 2001; 166(10): 6341 - 6348. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
