Circulation. 2001;104:1413-1418
doi: 10.1161/hc3601.095578
doi: 10.1161/hc3601.095578
(Circulation. 2001;104:1413.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Inhibition of Mannose-Binding Lectin Reduces Postischemic Myocardial Reperfusion Injury
From the Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Dr Gregory L. Stahl, CET&RI, Department of Anesthesia, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail gstahl{at}zeus.bwh.harvard.edu
Background—— Complement consists of a complex cascade of proteins involved in innate and adaptive immunity. The cascade can be activated through 3 distinct mechanisms, designated the classical, alternative, and lectin pathways. Although complement is widely accepted as participating in the pathophysiology of ischemia-reperfusion injury, the specific role of the lectin pathway has not been addressed.
Methods and Results—— Monoclonal antibodies (mAbs; P7E4 and 14C3.74, IgG1
isotypes) were raised against rat mannose-binding lectin (rMBL). Both mAbs recognized rMBL-A by Western analysis or surface plasmon resonance. P7E4, but not 14C3.74, exhibited a concentration-dependent inhibition of the lectin pathway, with maximal effect at 10 µg/mL. In vivo, rats were subjected to 30 minutes of left coronary artery occlusion and 4 hours of reperfusion. Complement C3 deposition was greatly attenuated in hearts pretreated with P7E4 compared with 14C3.74-treated hearts. Pretreatment with P7E4 (1 mg/kg) significantly reduced myocardial creatine kinase loss (48%), infarct size (39%), and neutrophil infiltration (47%) compared with 14C3.74-treated animals. In addition, P7E4 pretreatment significantly attenuated the expression of proinflammatory genes (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) after ischemia-reperfusion.
Conclusions—— The lectin complement pathway is activated after myocardial ischemia-reperfusion and leads to tissue injury. Blockade of the lectin pathway with inhibitory mAbs protects the heart from ischemia-reperfusion by reducing neutrophil infiltration and attenuating proinflammatory gene expression.
Key Words: ischemia • infarction • antibodies • cell adhesion molecules • inflammation
This article has been cited by other articles:
 |
|
 |
|
  M. N. Busche, V. Pavlov, K. Takahashi, and G. L. Stahl Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectin Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1853 - H1859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. La Bonte, B. Dokken, G. Davis-Gorman, G. L. Stahl, and P. F. McDonagh The mannose-binding lectin pathway is a significant contributor to reperfusion injury in the type 2 diabetic heart Diabetes and Vascular Disease Research, July 1, 2009; 6(3): 172 - 180. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Kulik, S. D. Fleming, C. Moratz, J. W. Reuter, A. Novikov, K. Chen, K. A. Andrews, A. Markaryan, R. J. Quigg, G. J. Silverman, et al. Pathogenic Natural Antibodies Recognizing Annexin IV Are Required to Develop Intestinal Ischemia-Reperfusion Injury J. Immunol., May 1, 2009; 182(9): 5363 - 5373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. La Bonte, G. Davis-Gorman, G. L. Stahl, and P. F. McDonagh Complement inhibition reduces injury in the type 2 diabetic heart following ischemia and reperfusion Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1282 - H1290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Marcheix, M. Carrier, C. Martel, M. Cossette, M. Pellerin, D. Bouchard, and L. P. Perrault Effect of Pericardial Blood Processing on Postoperative Inflammation and the Complement Pathways Ann. Thorac. Surg., February 1, 2008; 85(2): 530 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Roos, M. R. Daha, J. van Pelt, and S. P. Berger Mannose-binding lectin and the kidney Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3370 - 3377. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Szeplaki, L. Varga, J. Laki, E. Dosa, S. Rugonfalvi-Kiss, H. O. Madsen, Z. Prohaszka, A. Kocsis, P. Gal, A. Szabo, et al. Low C1-Inhibitor Levels Predict Early Restenosis After Eversion Carotid Endarterectomy Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2756 - 2762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Collard, S. K. Shernan, A. A. Fox, T. Bernig, S. J. Chanock, W. K. Vaughn, K. Takahashi, A. B. Ezekowitz, P. Jarolim, and S. C. Body The MBL2 'LYQA Secretor' Haplotype Is an Independent Predictor of Postoperative Myocardial Infarction in Whites Undergoing Coronary Artery Bypass Graft Surgery Circulation, September 11, 2007; 116(11_suppl): I-106 - I-112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Markiewski and J. D. Lambris The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight Am. J. Pathol., September 1, 2007; 171(3): 715 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Berger, A. Roos, M. J.K. Mallat, A. F.M. Schaapherder, I. I. Doxiadis, C. van Kooten, F. W. Dekker, M. R. Daha, and J. W. de Fijter Low Pretransplantation Mannose-Binding Lectin Levels Predict Superior Patient and Graft Survival after Simultaneous Pancreas-Kidney Transplantation J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2416 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Szabo, J. Laki, H. O. Madsen, E. Dosa, Z. Prohaszka, S. Rugonfalvi-Kiss, M. Kokai, G. Acsadi, I. Karadi, L. Entz, et al. Early Rise in Serum VEGF and PDGF Levels Predisposes Patients With a Normal MBL2 Genotype to Restenosis After Eversion Endarterectomy Stroke, August 1, 2007; 38(8): 2247 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Iwaki, K. Kanno, M. Takahashi, Y. Endo, N. J. Lynch, W. J. Schwaeble, M. Matsushita, M. Okabe, and T. Fujita Small Mannose-Binding Lectin-Associated Protein Plays a Regulatory Role in the Lectin Complement Pathway J. Immunol., December 15, 2006; 177(12): 8626 - 8632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Hansen, M.-A. Gall, L. Tarnow, S. Thiel, C. D. Stehouwer, C. G. Schalkwijk, H.-H. Parving, and A. Flyvbjerg Mannose-binding lectin and mortality in type 2 diabetes. Arch Intern Med, October 9, 2006; 166(18): 2007 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. Keller, S. I. van Leuven, M. C. Meuwese, N. J. Wareham, R. Luben, E. S. Stroes, C. E. Hack, M. Levi, K.-T. Khaw, and S. M. Boekholdt Serum Levels of Mannose-Binding Lectin and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2345 - 2350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Girardi, D. Yarilin, J. M. Thurman, V. M. Holers, and J. E. Salmon Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction J. Exp. Med., September 4, 2006; 203(9): 2165 - 2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Quaniers, J. Leruth, A. Albert, R. R. Limet, and J.-O. Defraigne Comparison of inflammatory responses after off-pump and on-pump coronary surgery using surface modifying additives circuit. Ann. Thorac. Surg., May 1, 2006; 81(5): 1683 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Patel, R. A.G. Smith, S. H. Sacks, and W. Zhou Therapeutic Strategy with a Membrane-Localizing Complement Regulator to Increase the Number of Usable Donor Organs after Prolonged Cold Storage J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1102 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. D. Riis, T. K. Hansen, S. Thiel, C. H. Gravholt, S. Gjedde, L. C. Gormsen, J. O. L. Jorgensen, J. Weeke, and N. Moller Thyroid hormone increases mannan-binding lectin levels Eur. J. Endocrinol., November 1, 2005; 153(5): 643 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Banz, O. M. Hess, S. C. Robson, D. Mettler, P. Meier, A. Haeberli, E. Csizmadia, E. Y. Korchagina, N. V. Bovin, and R. Rieben Locally targeted cytoprotection with dextran sulfate attenuates experimental porcine myocardial ischaemia/reperfusion injury Eur. Heart J., November 1, 2005; 26(21): 2334 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Ueng, C.-C. Hung, M.-L. Kuo, P.-K. Chan, S.-H. Hu, P.-C. Yang, and L. W. Chang Induction of Fibroblast Growth Factor-9 and Interleukin-1{alpha} Gene Expression by Motorcycle Exhaust Particulate Extracts and Benzo(a)pyrene in Human Lung Adenocarcinoma Cells Toxicol. Sci., October 1, 2005; 87(2): 483 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Fiane, T. Ueland, S. Simonsen, H. Scott, K. Endresen, L. Gullestad, O. R. Geiran, G. Haraldsen, L. Heggelund, A. K. Andreassen, et al. Low mannose-binding lectin and increased complement activation correlate to allograft vasculopathy, ischaemia, and rejection after human heart transplantation Eur. Heart J., August 2, 2005; 26(16): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Walsh, T. Bourcier, K. Takahashi, L. Shi, M. N. Busche, R. P. Rother, S. D. Solomon, R. A. B. Ezekowitz, and G. L. Stahl Mannose-Binding Lectin Is a Regulator of Inflammation That Accompanies Myocardial Ischemia and Reperfusion Injury J. Immunol., July 1, 2005; 175(1): 541 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Hart, K. A. Ceonzo, L. A. Shaffer, K. Takahashi, R. P. Rother, W. R. Reenstra, J. A. Buras, and G. L. Stahl Gastrointestinal Ischemia-Reperfusion Injury Is Lectin Complement Pathway Dependent without Involving C1q J. Immunol., May 15, 2005; 174(10): 6373 - 6380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hovind, T. K. Hansen, L. Tarnow, S. Thiel, R. Steffensen, A. Flyvbjerg, and H.-H. Parving Mannose-Binding Lectin as a Predictor of Microalbuminuria in Type 1 Diabetes: An Inception Cohort Study Diabetes, May 1, 2005; 54(5): 1523 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rugonfalvi-Kiss, E. Dosa, H. O. Madsen, V. Endresz, Z. Prohaszka, J. Laki, I. Karadi, E. Gonczol, L. Selmeci, L. Romics, et al. High Rate of Early Restenosis After Carotid Eversion Endarterectomy in Homozygous Carriers of the Normal Mannose-Binding Lectin Genotype Stroke, May 1, 2005; 36(5): 944 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. de Vries, S. J. Walter, C. J. Peutz-Kootstra, T. G.A.M. Wolfs, L.W. E. van Heurn, and W. A. Buurman The Mannose-Binding Lectin-Pathway Is Involved in Complement Activation in the Course of Renal Ischemia-Reperfusion Injury Am. J. Pathol., November 1, 2004; 165(5): 1677 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Hansen, L. Tarnow, S. Thiel, R. Steffensen, C. D. Stehouwer, C. G. Schalkwijk, H.-H. Parving, and A. Flyvbjerg Association Between Mannose-Binding Lectin and Vascular Complications in Type 1 Diabetes Diabetes, June 1, 2004; 53(6): 1570 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamada, T. Miwa, J. Liu, M. Nangaku, and W.-C. Song Critical Protection from Renal Ischemia Reperfusion Injury by CD55 and CD59 J. Immunol., March 15, 2004; 172(6): 3869 - 3875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Best, M. Davidson, K. E. North, J. W. MacCluer, Y. Zhang, E. T. Lee, B. V. Howard, S. DeCroo, and R. E. Ferrell Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians: The Strong Heart Study Circulation, February 3, 2004; 109(4): 471 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Hansen, S. Thiel, S. T. Knudsen, C. H. Gravholt, J. S. Christiansen, C. E. Mogensen, and P. L. Poulsen Elevated Levels of Mannan-Binding Lectin in Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4857 - 4861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Quigg Complement and the Kidney J. Immunol., October 1, 2003; 171(7): 3319 - 3324. [Full Text] [PDF]
|
|
|
|
|
|
A. E. Fiane, V. Videm, P. S. Lingaas, L. Heggelund, E. W. Nielsen, O. R. Geiran, M. Fung, and T. E. Mollnes Mechanism of Complement Activation and Its Role in the Inflammatory Response After Thoracoabdominal Aortic Aneurysm Repair Circulation, August 19, 2003; 108(7): 849 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. de Vries, R. A. Matthijsen, A. A. J. H. M. van Bijnen, T. G. A. M. Wolfs, and W. A. Buurman Lysophosphatidic Acid Prevents Renal Ischemia-Reperfusion Injury by Inhibition of Apoptosis and Complement Activation Am. J. Pathol., July 1, 2003; 163(1): 47 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. de Vries, J. Kohl, W. K. G. Leclercq, T. G. A. M. Wolfs, A. A. J. H. M. van Bijnen, P. Heeringa, and W. A. Buurman Complement Factor C5a Mediates Renal Ischemia-Reperfusion Injury Independent from Neutrophils J. Immunol., April 1, 2003; 170(7): 3883 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Riedemann and P. A. Ward Complement in Ischemia Reperfusion Injury Am. J. Pathol., February 1, 2003; 162(2): 363 - 367. [Full Text] [PDF]
|
|
|
|
|
|
G. L. Stahl, Y. Xu, L. Hao, M. Miller, J. A. Buras, M. Fung, and H. Zhao Role for the Alternative Complement Pathway in Ischemia/Reperfusion Injury Am. J. Pathol., February 1, 2003; 162(2): 449 - 455. [Abstract] [Full Text] [PDF]
|
|