Abstract
Collectin kidney 1 (CL-K1) is a recently identified collectin that is synthesized in most organs and circulates in blood. CL-K1 is an innate immune molecule that may play a significant role in host defense. As some collectins also play a role in coagulation, we hypothesized that an effect of CL-K1 may be apparent in disseminated intravascular coagulation (DIC), a gross derangement of the coagulation system that occurs in the setting of profound activation of the innate immune system. DIC is a grave medical condition with a high incidence of multiple organ failure and high mortality and yet there are no reliable biomarkers or risk factors. In our present study, we measured plasma CL-K1 concentration in a total of 659 specimens, including 549 DIC patients, 82 non-DIC patients and 27 healthy volunteers. The median plasma CL-K1 levels in these cohorts were 424, 238 and 245 ng/ml, respectively, with no significant difference in the latter two groups. The incidence of elevated plasma CL-K1 was significantly higher in the DIC patients compared to the non-DIC patients, resulting in an odds ratio of 1.929 (confidence interval 1.041–3.866). Infection, renal diseases, respiratory diseases, and cardiac diseases were more frequently observed in the DIC group than in the non-DIC group. In the DIC group, vascular diseases were associated with elevated plasma CL-K1 levels while age and acute illness had little effect on plasma CL-K1 levels. Independent of DIC, elevated plasma CL-K1 levels were associated with respiratory disease and coagulation disorders. These results suggest that specific diseases may affect CL-K1 synthesis in an organ dependent manner and that elevated plasma CL-K1 levels are associated with the presence of DIC. Further investigations in cohorts of patients are warranted. We propose that elevated plasma CL-K1 may be a new useful risk factor and possibly biomarker for the prediction of developing DIC.
Similar content being viewed by others
References
Thiel S, Takahashi K (2013) Collectins. In: Encyclopedia of life sciences. Wiley, Chichester, UK
Keshi H, Sakamoto T, Kawai T, Ohtani K, Katoh T, Jang SJ, Motomura W, Yoshizaki T, Fukuda M, Koyama S, Fukuzawa J, Fukuoh A, Yoshida I, Suzuki Y, Wakamiya N (2006) Identification and characterization of a novel human collectin CL-K1. Microbiol Immunol 50(12):1001–1013
Ohtani K, Suzuki Y, Wakamiya N (2012) Biological functions of the novel collectins CL-L1, CL-K1, and CL-P1. J Biomed Biotechnol 2012:493945. doi:10.1155/2012/493945
Thiel S (2007) Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol 44(16):3875–3888
Takahashi K (2008) Lessons learned from murine models of mannose-binding lectin deficiency. Biochem Soc Trans 36(Pt 6):1487–1490. doi:10.1042/BST0361487
Yoshizaki T, Ohtani K, Motomura W, Jang SJ, Mori K, Kitamoto N, Yoshida I, Suzuki Y, Wakamiya N (2012) Comparison of human blood concentrations of collectin kidney 1 and mannan-binding lectin. J Biochem 151(1):57–64. doi:10.1093/jb/mvr114
Selman L, Henriksen ML, Brandt J, Palarasah Y, Waters A, Beales PL, Holmskov U, Jorgensen TJ, Nielsen C, Skjodt K, Hansen S (2012) An enzyme-linked immunosorbent assay (ELISA) for quantification of human collectin 11 (CL-11, CL-K1). J Immunol Methods 375(1–2):182–188. doi:10.1016/j.jim.2011.10.010
Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC (2000) Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods 241(1–2):33–42
Garred P, Larsen F, Madsen HO, Koch C (2003) Mannose-binding lectin deficiency—revisited. Mol Immunol 40(2–4):73–84
Uemura K, Saka M, Nakagawa T, Kawasaki N, Thiel S, Jensenius JC, Kawasaki T (2002) L-MBP is expressed in epithelial cells of mouse small intestine. J Immunol 169(12):6945–6950
Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, Kenny J, Waters A, Jenkins D, Kaissi AA, Leal GF, Dallapiccola B, Carnevale F, Bitner-Glindzicz M, Lees M, Hennekam R, Stanier P, Burns AJ, Peeters H, Alkuraya FS, Beales PL (2011) Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat Genet 43(3):197–203. doi:10.1038/ng.757
Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, Jonasson M, Skjoedt MO, Nielsen O, Hartshorn K, Jorgensen TJ, Skjodt K, Holmskov U (2010) Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol 185(10):6096–6104. doi:10.4049/jimmunol.1002185
Takahashi K, Chang WC, Takahashi M, Pavlov V, Ishida Y, La Bonte L, Shi L, Fujita T, Stahl GL, Van Cott EM (2011) Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation. Immunobiology 216(1–2):96–102. doi:10.1016/j.imbio.2010.02.005
Sekine H, Takahashi M, Iwaki D, Fujita T (2013) The role of MASP-1/3 in complement activation. Adv Exp Med Biol 735:41–53
Gulla KC, Gupta K, Krarup A, Gal P, Schwaeble WJ, Sim RB, O’Connor CD, Hajela K (2010) Activation of mannan-binding lectin-associated serine proteases leads to generation of a fibrin clot. Immunology 129(4):482–495. doi:10.1111/j.1365-2567.2009.03200.x
Presanis JS, Hajela K, Ambrus G, Gal P, Sim RB (2004) Differential substrate and inhibitor profiles for human MASP-1 and MASP-2. Mol Immunol 40(13):921–929
Toh CH, Ticknor LO, Downey C, Giles AR, Paton RC, Wenstone R (2003) Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation. Intensive Care Med 29(1):55–61. doi:10.1007/s00134-002-1557-2
Smith EY, Charles LA, Van Cott EM (2004) Biphasic activated partial thromboplastin time waveform and adverse events in non-intensive care unit patients. Am J Clin Pathol 121(1):138–141. doi:10.1309/W4F7-892W-JE6Y-1W7Y
Penner JA (1998) Disseminated intravascular coagulation in patients with multiple organ failure of non-septic origin. Semin Thromb Hemost 24(1):45–52. doi:10.1055/s-2007-995822
Matsumoto T, Wada H, Nishioka Y, Nishio M, Abe Y, Nishioka J, Kamikura Y, Sase T, Kaneko T, Houdijk WP, Nobori T, Shiku H (2006) Frequency of abnormal biphasic aPTT clot waveforms in patients with underlying disorders associated with disseminated intravascular coagulation. Clin Appl Thromb Hemost 12(2):185–192
Toh CH, Samis J, Downey C, Walker J, Becker L, Brufatto N, Tejidor L, Jones G, Houdijk W, Giles A, Koschinsky M, Ticknor LO, Paton R, Wenstone R, Nesheim M (2002) Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation. Blood 100(7):2522–2529. doi:10.1182/blood.V100.7.2522
Downey C, Kazmi R, Toh CH (1998) Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis. Thromb Haemost 80(1):65–69
Krause RD, Anand VD, Gruemer HD, Willke TA (1975) The impact of laboratory error on the normal range: a Bayesian model. Clin Chem 21(3):321–324
Hapke M, Patil K (1981) The establishment of normal limits for serum proteins measured by the rate nephelometer. Concepts of normality revisited. Hum Pathol 12(11):1011–1015
Stemerman MB (1985) Coagulation in the elderly. Clin Geriatr Med 1(4):869–885
La Bonte LR, Pavlov VI, Tan YS, Takahashi K, Takahashi M, Banda NK, Zou C, Fujita T, Stahl GL (2012) Mannose-binding lectin-associated serine protease-1 is a significant contributor to coagulation in a murine model of occlusive thrombosis. J Immunol 188(2):885–891. doi:10.4049/jimmunol.1102916
Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U, Reid KB, Jensenius JC (1997) A second serine protease associated with mannan-binding lectin that activates complement. Nature 386(6624):506–510
Matsushita M (2009) Ficolins: complement-activating lectins involved in innate immunity. J Innate Immun 2(1):24–32. doi:10.1159/000228160
Takahashi K, Ezekowitz RA (2005) The role of the mannose-binding lectin in innate immunity. Clin Infect Dis 41(Suppl 7):S440–S444
Moller-Kristensen M, Hamblin MR, Thiel S, Jensenius JC, Takahashi K (2007) Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice. J Invest Dermatol 127(6):1524–1531
Chang WC, White MR, Moyo P, McClear S, Thiel S, Hartshorn KL, Takahashi K (2010) Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection. BMC Immunol 11(1):64. doi:10.1186/1471-2172-11-64
Larvie M, Shoup T, Chang WC, Chigweshe L, Hartshorn K, White MR, Stahl GL, Elmaleh DR, Takahashi K (2012) Mannose-binding lectin binds to amyloid beta protein and modulates inflammation. J Biomed Biotechnol 2012:929803. doi:10.1155/2012/929803
Ip WK, Lau YL, Chan SY, Mok CC, Chan D, Tong KK, Lau CS (2000) Mannose-binding lectin and rheumatoid arthritis in southern Chinese. Arthritis Rheum 43(8):1679–1687
Motomura W, Yoshizaki T, Ohtani K, Okumura T, Fukuda M, Fukuzawa J, Mori K, Jang SJ, Nomura N, Yoshida I, Suzuki Y, Kohgo Y, Wakamiya N (2008) Immunolocalization of a novel collectin CL-K1 in murine tissues. J Histochem Cytochem 56(3):243–252. doi:10.1369/jhc.7A7312.2007
Acknowledgments
The authors thank laboratory personnel in the Coagulation Laboratory at the Massachusetts General Hospital. The work was supported in part by NIH Grant U01-074503 (K.T.) and Grants-in-Aid for Scientific Research of the Japan of Ministry of Education, Culture, Sports, Science, and Technology, 19390227 (N.W). This work was also supported by grants from Fuso Pharmaceutical Industry, Co., the Smoking Research Foundation, and the Mizutani foundation for glycoscience (N.W).
Author information
Authors and Affiliations
Corresponding author
Additional information
Elizabeth M. Van Cott and Nobutaka Wakamiya are co-senior authors.
Rights and permissions
About this article
Cite this article
Takahashi, K., Ohtani, K., Larvie, M. et al. Elevated plasma CL-K1 level is associated with a risk of developing disseminated intravascular coagulation (DIC). J Thromb Thrombolysis 38, 331–338 (2014). https://doi.org/10.1007/s11239-013-1042-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11239-013-1042-5