Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collectin-11 (CL-11) is a pattern recognition molecule of the lectin pathway of complement with diverse functions spanning from host defense to embryonic development. CL-11 is found in the circulation in heterocomplexes with the homologous collectin-10 (CL-10). Abnormal CL-11 plasma levels are associated with the presence of disseminated intravascular coagulation, urinary schistosomiasis, and congenital disorders. Although there has been a marked development in the characterization of CL-11 there is still a scarcity of clinical tools for its analysis. Thus, we generated monoclonal antibodies and developed a quantitative ELISA to measure CL-11 in the circulation. The antibodies were screened against recombinant CL-11 and validated by ELISA and immunoprecipitation of serum and plasma. The best candidates were pairwise compared to develop a quantitative ELISA. The assay was validated regarding its sensitivity, reproducibility, and dilution linearity, demonstrating a satisfactory variability over a working range of 0.29-18.75 ng/ml. The mean plasma concentration of CL-11 in healthy controls was determined to be 289.4 ng/ml (range 143.2-459.4 ng/ml), highly correlated to the levels of CL/10/11 complexes (r = 0.729). Plasma CL-11 and CL-10/11 co-migrated in size exclusion chromatography as two major complexes of ~400 and >600 kDa. Furthermore, we observed a significant decrease at admission in CL-11 plasma levels in patients admitted to intensive care with systemic inflammatory response syndrome. By using the in-house antibodies and recombinant CL-11, we found that CL-11 can bind to zymosan independently of calcium by a separate site from the carbohydrate-binding region. Finally, we showed that CL-11/MASP-2 complexes trigger C4b deposition on zymosan. In conclusion, we have developed a specific and sensitive ELISA to investigate the ever-expanding roles of CL-11 in health and disease and shown a novel interaction between CL-11 and zymosan.
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PMID:Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1). 3032 15

Collectin LK (CL-LK) is a recently described collectin complex, which upon binding to microbial glycoconjugates, activates the lectin pathway of the complement system, and thereby contributes to the removal of invading microorganisms. The complex consists of the two collectins; Collectin K1 (kidney 1 alias CL-11) and Collectin L1 (liver 1 alias CL-10). At present, most efforts have been made on the characterization of CL-K1, and little is known about the function of CL-L1 and its association with diseases. Deficiency of either of the two collectins is associated with the developmental syndrome 3MC, whereas increased plasma levels of CL-K1 are associated with disseminated intravascular coagulation. Using CL-LK purified from human plasma as an immunogen, we succeed in generating seven monoclonal antibodies (mAbs) with specificity for CL-L1. All seven mAbs recognize both native and recombinant CL-L1. In addition, four of the mAbs were successful in immunohistochemical detection of CL-L1 in human tissues. To our knowledge, these are the first mAbs specific for human native CL-L1 described in the literature, and we expect them to be of great importance in characterizing the function of CL-L1, as well as for the study of CL-L1's association with disease.
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PMID:Novel Monoclonal Antibodies Against Native Human Collectin L1, Using the Heteromeric Complex CL-LK as Immunogen. 3036 27