Increased Plasma Mannose Binding Lectin Levels Are Associated with Bronchiolitis Obliterans After Lung Transplantation

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2012 Jul 6

PMID 22762710

Citations 5

Authors

Steven J Budd

Robert M Aris

Ayorinde A Medaiyese

Stephen L Tilley

Isabel P Neuringer

Affiliations

Soon will be listed here.

Abstract

Background: Long-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue samples from explanted lungs with BOS, and assessed MBL and complement proteins in plasma post-lung transplantation relative to BOS staging.

Methods: MBL was detected by immunohistochemistry lung tissue at the time of cold ischemia and in samples with BOS. MBL was assayed in the peripheral blood of 66 lung transplant patients transplanted between 1990-2007.

Results: MBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant > 5 years (n = 33), had significantly lower levels of MBL in the blood compared to lung transplant patients < 5 years with BOS Op-3 (n = 17), 1738 ± 250 ng/ml vs 3198 ± 370 ng/ml, p = 0.027, and similar levels to lung transplant patients < 5 years with BOS 0 (n = 16), 1738 ± 250 ng/ml vs 1808 ± 345 ng/ml. MBL levels in all BOS 0 (n = 30) vs. all BOS Op-3 (n = 36) were 1378 ± 275 ng/ml vs. 2578 ± 390 ng/ml, p = 0.001, respectively. C3 plasma levels in BOS 0 (n = 30) vs. BOS Op-3 (n = 36) were 101 ± 19.8 mg/ml vs. 114 ± 25.2 mg/ml, p = 0.024, respectively.

Conclusions: MBL localizes within the lung during graft ischemia and BOS, higher levels of plasma MBL are associated with BOS Op-3 and < 5 years post-transplant, and higher level of plasma complement protein C3 was associated with BOS Op-3 clinical status. MBL may serve as a biomarker for poorer outcome post-lung transplantation.

Citing Articles

Effector immune cells in chronic lung allograft dysfunction: A systematic review.

Bos S, Filby A, Vos R, Fisher A Immunology. 2022; 166(1):17-37.

PMID: 35137398 PMC: 9426626. DOI: 10.1111/imm.13458.

Mannose-Binding Lectin: Biologic Characteristics and Role in the Susceptibility to Infections and Ischemia-Reperfusion Related Injury in Critically Ill Neonates.

Auriti C, Prencipe G, Moriondo M, Bersani I, Bertaina C, Mondi V J Immunol Res. 2017; 2017:7045630.

PMID: 28246614 PMC: 5299167. DOI: 10.1155/2017/7045630.

Protein-DNA array-based identification of transcription factor activities differentially regulated in obliterative bronchiolitis.

Dong M, Wang X, Zhao H, Zhao Y, Jing Y, Yuan J Int J Clin Exp Pathol. 2015; 8(6):7140-8.

PMID: 26261607 PMC: 4525941.

Mannan-binding lectin in cardiovascular disease.

Pagowska-Klimek I, Cedzynski M Biomed Res Int. 2014; 2014:616817.

PMID: 24877121 PMC: 4022110. DOI: 10.1155/2014/616817.

Bronchiolitis obliterans syndrome: the Achilles' heel of lung transplantation.

Samuel Weigt S, DerHovanessian A, Wallace W, Lynch 3rd J, Belperio J Semin Respir Crit Care Med. 2013; 34(3):336-51.

PMID: 23821508 PMC: 4768744. DOI: 10.1055/s-0033-1348467.

References

Ribeiro L, Tripp R, Rossi L, Bonini Palma P, Yokosawa J, Mantese O . Serum mannose-binding lectin levels are linked with respiratory syncytial virus (RSV) disease. J Clin Immunol. 2007; 28(2):166-73. DOI: 10.1007/s10875-007-9141-8. View

Zhang M, Carroll M . Natural antibody mediated innate autoimmune response. Mol Immunol. 2006; 44(1-3):103-10. DOI: 10.1016/j.molimm.2006.06.022. View

Thiel S, Vorup-Jensen T, Stover C, Schwaeble W, Laursen S, Poulsen K . A second serine protease associated with mannan-binding lectin that activates complement. Nature. 1997; 386(6624):506-10. DOI: 10.1038/386506a0. View

Bernig T, Taylor J, FOSTER C, Staats B, Yeager M, Chanock S . Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection. Genes Immun. 2004; 5(6):461-76. DOI: 10.1038/sj.gene.6364116. View

Green D, Ferguson T, Zitvogel L, Kroemer G . Immunogenic and tolerogenic cell death. Nat Rev Immunol. 2009; 9(5):353-63. PMC: 2818721. DOI: 10.1038/nri2545. View

Walsh M, Bourcier T, Takahashi K, Shi L, Busche M, Rother R . Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol. 2005; 175(1):541-6. DOI: 10.4049/jimmunol.175.1.541. View

Nauta A, Raaschou-Jensen N, Roos A, Daha M, Madsen H, Borrias-Essers M . Mannose-binding lectin engagement with late apoptotic and necrotic cells. Eur J Immunol. 2003; 33(10):2853-63. DOI: 10.1002/eji.200323888. View

Imai N, Nishi S, Alchi B, Ueno M, Fukase S, Arakawa M . Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition. Nephrol Dial Transplant. 2006; 21(9):2589-95. DOI: 10.1093/ndt/gfl210. View

de Vries B, Walter S, Peutz-Kootstra C, Wolfs T, van Heurn L, Buurman W . The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury. Am J Pathol. 2004; 165(5):1677-88. PMC: 1618654. DOI: 10.1016/S0002-9440(10)63424-4. View

10.

Berger S, Roos A, Mallat M, Fujita T, De Fijter J, Daha M . Association between mannose-binding lectin levels and graft survival in kidney transplantation. Am J Transplant. 2005; 5(6):1361-6. DOI: 10.1111/j.1600-6143.2005.00841.x. View

11.

Zhang M, Takahashi K, Alicot E, Vorup-Jensen T, Kessler B, Thiel S . Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol. 2006; 177(7):4727-34. DOI: 10.4049/jimmunol.177.7.4727. View

12.

Hodge S, Dean M, Hodge G, Holmes M, Reynolds P . Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2011; 30(5):589-95. DOI: 10.1016/j.healun.2011.01.710. View

13.

Aoyagi Y, Adderson E, Rubens C, Bohnsack J, Min J, Matsushita M . L-Ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway. Infect Immun. 2007; 76(1):179-88. PMC: 2223634. DOI: 10.1128/IAI.00837-07. View

14.

Nadar S, Lip G . New insights into complement C3 and inflammation in hypertension. J Hum Hypertens. 2007; 21(4):261-3. DOI: 10.1038/sj.jhh.1002160. View

15.

Angaswamy N, Saini D, Ramachandran S, Nath D, Phelan D, Hachem R . Development of antibodies to human leukocyte antigen precedes development of antibodies to major histocompatibility class I-related chain A and are significantly associated with development of chronic rejection after human lung transplantation. Hum Immunol. 2010; 71(6):560-5. PMC: 2874120. DOI: 10.1016/j.humimm.2010.02.021. View

16.

Ibernon M, Moreso F, Moreno J, Bestard O, Cruzado J, Grinyo J . Low serum mannose-binding lectin as a risk factor for new onset diabetes mellitus after renal transplantation. Transplantation. 2009; 88(2):272-8. DOI: 10.1097/TP.0b013e3181ac8e36. View

17.

Hecker L, Edwards A, Ryu E, Tosakulwong N, Baratz K, Brown W . Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. Hum Mol Genet. 2009; 19(1):209-15. PMC: 2792151. DOI: 10.1093/hmg/ddp472. View

18.

Murata K, Fox-Talbot K, Qian Z, Takahashi K, Stahl G, Baldwin 3rd W . Synergistic deposition of C4d by complement-activating and non-activating antibodies in cardiac transplants. Am J Transplant. 2007; 7(11):2605-14. DOI: 10.1111/j.1600-6143.2007.01971.x. View

19.

Corris P . Lung transplantation. Bronchiolitis obliterans syndrome. Chest Surg Clin N Am. 2003; 13(3):543-57. DOI: 10.1016/s1052-3359(03)00052-8. View

20.

Belperio J, Samuel Weigt S, Fishbein M, Lynch 3rd J . Chronic lung allograft rejection: mechanisms and therapy. Proc Am Thorac Soc. 2009; 6(1):108-21. DOI: 10.1513/pats.200807-073GO. View