Change of surfactant protein D and A after renal ischemia reperfusion injury

Autoři: Islam Md Imtiazul aff001;  Redwan Asma aff001;  Ji-Hye Lee aff002;  Nam-Jun Cho aff003;  Samel Park aff003;  Ho-Yeon Song aff001;  Hyo-Wook Gil aff003
Působiště autorů: Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea aff001;  Department of Pathology, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea aff002;  Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Acute kidney injury (AKI) is associated with widespread effects on distant organs, including the lungs. Surfactant protein (SP)-A and SP-D are members of the C-type lectin family, which plays a critical role in host defense and regulation of inflammation in a variety of infections. Serum levels of SP-A and SP-D are markers to reflect lung injury in acute respiratory distress syndrome, idiopathic pulmonary fibrosis, and sarcoidosis. We investigated the change of lung-specific markers, including SP-A and SP-D in an AKI mice model. We studied C57BL/6J mice 4 and 24 hours after an episode of ischemic AKI (23 min of renal pedicle clamping and then reperfusion); numerous derangements were present, including SP-A, SP-D, and lung tight-junction protein. Neutrophil infiltration and apoptosis in the lungs increased in ischemic AKI. Receptor for advanced glycation end products (RAGE) in the lungs, a marker of pneumocyte I, was not changed. Lung tight-junction proteins, particularly claudin-4, claudin-18, and anti-junctional adhesion molecule 1 (JAMA-1), were reduced in 24 hours after AKI. Serum SP-A and SP-D significantly increased in ischemic AKI. SP-A and SP-D in the lungs did not increase in ischemic AKI. The immunohistochemistry showed that the expression of SP-A and SP-D was intact in ischemic AKI. SP-A and SP-D in the kidneys were significantly higher in AKI than in the sham. These patterns of SP-A and SP-D in the kidneys were similar to those of serum. AKI induces apoptosis and inflammation in the lungs. Serum SP-A and SP-D increased in ischemic AKI, but these could have originated from the kidneys. So serum SP-A and SP-D could not reflect lung injury in AKI. Further study is needed to reveal how a change in lung tight-junction protein could influence the prognosis in patients with AKI.

Klíčová slova:

Apoptosis – Cytokines – Inflammation – Kidneys – Neutrophils – Reperfusion – Renal ischemia


1. Wald R, McArthur E, Adhikari NK, Bagshaw SM, Burns KE, Garg AX, et al. Changing incidence and outcomes following dialysis-requiring acute kidney injury among critically ill adults: a population-based cohort study. Am J Kidney Dis. 2015;65(6):870–7. doi: 10.1053/j.ajkd.2014.10.017 25533599

2. Park S, Lee S, Jo HA, Han K, Kim Y, An JN, et al. Epidemiology of continuous renal replacement therapy in Korea: Results from the National Health Insurance Service claims database from 2005 to 2016. Kidney Res Clin Pract. 2018;37(2):119–29. doi: 10.23876/j.krcp.2018.37.2.119 29971207

3. Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med. 2002;30(9):2051–8. doi: 10.1097/00003246-200209000-00016 12352040

4. Lee SA, Cozzi M, Bush EL, Rabb H. Distant Organ Dysfunction in Acute Kidney Injury: A Review. Am J Kidney Dis. 2018;72(6):846–56. doi: 10.1053/j.ajkd.2018.03.028 29866457

5. Lee J, Ko YS, Lee HY, Yang J, Oh S, Jo SK, et al. The role of senescence of bone marrow cells in acute kidney injury. Kidney Res Clin Pract. 2019;38(1):25–32. doi: 10.23876/j.krcp.18.0114 30798585

6. Zhang J, Ankawi G, Sun J, Digvijay K, Yin Y, Rosner MH, et al. Gut-kidney crosstalk in septic acute kidney injury. Crit Care. 2018;22(1):117. doi: 10.1186/s13054-018-2040-y 29724256

7. Fox BM, Gil HW, Kirkbride-Romeo L, Bagchi RA, Wennersten SA, Haefner KR, et al. Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice. Kidney Int. 2019;95(3):590–610. doi: 10.1016/j.kint.2018.10.020 30709662

8. Doi K, Rabb H. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney Int. 2016;89(3):555–64. doi: 10.1016/j.kint.2015.11.019 26880452

9. Faubel S, Edelstein CL. Mechanisms and mediators of lung injury after acute kidney injury. Nat Rev Nephrol. 2016;12(1):48–60. doi: 10.1038/nrneph.2015.158 26434402

10. Andres-Hernando A, Okamura K, Bhargava R, Kiekhaefer CM, Soranno D, Kirkbride-Romeo LA, et al. Circulating IL-6 upregulates IL-10 production in splenic CD4(+) T cells and limits acute kidney injury-induced lung inflammation. Kidney Int. 2017;91(5):1057–69. doi: 10.1016/j.kint.2016.12.014 28214022

11. Ahuja N, Andres-Hernando A, Altmann C, Bhargava R, Bacalja J, Webb RG, et al. Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice. Am J Physiol Renal Physiol. 2012;303(6):F864–72. doi: 10.1152/ajprenal.00025.2012 22791336

12. Altmann C, Ahuja N, Kiekhaefer CM, Andres Hernando A, Okamura K, Bhargava R, et al. Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury. Kidney Int. 2017;92(2):365–76. doi: 10.1016/j.kint.2017.01.020 28318621

13. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58–68. doi: 10.1038/nri1528 15630429

14. Park J, Pabon M, Choi AMK, Siempos II, Fredenburgh LE, Baron RM, et al. Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome: validation in US and Korean cohorts. BMC Pulm Med. 2017;17(1):204. doi: 10.1186/s12890-017-0532-1 29246207

15. Determann RM, Royakkers AA, Haitsma JJ, Zhang H, Slutsky AS, Ranieri VM, et al. Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients. BMC Pulm Med. 2010;10:6. doi: 10.1186/1471-2466-10-6 20158912

16. Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, et al. Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med. 2000;162(3 Pt 1):1109–14.

17. Hoke TS, Douglas IS, Klein CL, He Z, Fang W, Thurman JM, et al. Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. J Am Soc Nephrol. 2007;18(1):155–64. doi: 10.1681/ASN.2006050494 17167117

18. Eddy WE, Gong KQ, Bell B, Parks WC, Ziegler SF, Manicone AM. Stat5 Is Required for CD103(+) Dendritic Cell and Alveolar Macrophage Development and Protection from Lung Injury. J Immunol. 2017;198(12):4813–22. doi: 10.4049/jimmunol.1601777 28500076

19. Freitas SH, Doria RGS, Bueno RS, Rocha WB, Filho JRE, Moraes JRE, et al. Evaluation of potential changes in liver and lung tissue of rats in an ischemia-reperfusion injury model (modified pringle maneuver). PLoS One. 2017;12(6):e0178665. doi: 10.1371/journal.pone.0178665 28604841

20. Ko GJ, Rabb H, Hassoun HT. Kidney-lung crosstalk in the critically ill patient. Blood Purif. 2009;28(2):75–83. doi: 10.1159/000218087 19439927

21. Gil HW, Oh MH, Woo KM, Lee EY, Oh MH, Hong SY. Relationship between pulmonary surfactant protein and lipid peroxidation in lung injury due to paraquat intoxication in rats. Korean J Intern Med. 2007;22(2):67–72. doi: 10.3904/kjim.2007.22.2.67 17616020

22. Sugahara K, Iyama K, Sano K, Kuroki Y, Akino T, Matsumoto M. Overexpression of surfactant protein SP-A, SP-B, and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury. Lab Invest. 1996;74(1):209–20. 8569184

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2019 Číslo 12
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