60 research outputs found
Biological Functions of the Novel Collectins CL-L1, CL-K1, and CL-P1
Collectins are characterized by a collagen-like sequence and a carbohydrate recognition domain and are members of the vertebrate C-type lectin superfamily. Recently, “novel collectins”, different from “classical collectins” consisting of mannan-binding lectin (MBL) and surfactant proteins A and D (SP-A and SP-D), have been found by reverse genetics. These “novel collectins” consist of collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1), and collectin placenta 1 (CL-P1) and are encoded by three separate genes. Experimental findings on human and animal collectins have shown that both novel collectins and classical collectins play an important role in innate immunity. Based on our recent results and those of others, in this paper, we summarize the new biological functions of these novel collectins in embryonic morphogenesis and development
Guideline for Hereditary Angioedema (HAE) 2010 by the Japanese Association for Complement Research - Secondary Publication
ABSTRACTThis guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements
Molecular basis of sugar recognition by collectin-K1 and the effects of mutations associated with 3MC syndrome
Background Collectin-K1 (CL-K1, or CL-11) is a multifunctional Ca2+-dependent lectin with roles in innate immunity, apoptosis and embryogenesis. It binds to carbohydrates on pathogens to activate the lectin pathway of complement and together with its associated serine protease MASP-3 serves as a guidance cue for neural crest development. High serum levels are associated with disseminated intravascular coagulation, where spontaneous clotting can lead to multiple organ failure. Autosomal mutations in the CL-K1 or MASP-3 genes cause a developmental disorder called 3MC (Carnevale, Mingarelli, Malpuech and Michels) syndrome, characterised by facial, genital, renal and limb abnormalities. One of these mutations (Gly204Ser in the CL-K1 gene) is associated with undetectable levels of protein in the serum of affected individuals. Results In this study, we show that CL-K1 primarily targets a subset of high-mannose oligosaccharides present on both self- and non-self structures, and provide the structural basis for its ligand specificity. We also demonstrate that three disease-associated mutations prevent secretion of CL-K1 from mammalian cells, accounting for the protein deficiency observed in patients. Interestingly, none of the mutations prevent folding nor oligomerization of recombinant fragments containing the mutations in vitro. Instead, they prevent Ca2+ binding by the carbohydrate-recognition domains of CL-K1. We propose that failure to bind Ca2+ during biosynthesis leads to structural defects that prevent secretion of CL-K1, thus providing a molecular explanation of the genetic disorder. Conclusions We have established the sugar specificity of CL-K1 and demonstrated that it targets high-mannose oligosaccharides on self- and non-self structures via an extended binding site which recognises the terminal two mannose residues of the carbohydrate ligand. We have also shown that mutations associated with a rare developmental disorder called 3MC syndrome prevent the secretion of CL-K1, probably as a result of structural defects caused by disruption of Ca2+ binding during biosynthesis
Changes in Mannose-Binding Lectin and Collectin Kidney 1 Levels in Sepsis Patients With and Without Disseminated Intravascular Coagulation
In sepsis, systemic coagulation activation frequently causes disseminated intravascular coagulation (DIC), and the uncontrolled activation of the complement system can induce multiple organ dysfunction and poor prognosis. This study aimed to examine the association of DIC with levels of collectin kidney 1 (CL-K1), a novel collectin of the complement system, and mannose-binding lectin (MBL), a classical-type collectin in patients with sepsis. We collected blood samples prospectively from adult patients with sepsis admitted to the intensive care unit (ICU) from day 1 (admission) to day 5. The CL-K1 and MBL levels were measured by enzyme-linked immunosorbent assay, and DIC was diagnosed by using a scoring algorithm. The correlation of CL-K1 and MBL levels with other coagulation markers was analyzed. There were 37 patients with DIC (DIC group) and 15 without DIC (non-DIC group). Compared to the non-DIC group, the DIC group had more severe conditions and higher mortality. During the 5 days after ICU admission, plasma CL-K1 levels were similar between the groups, but plasma MBL levels were significantly lower in the DIC group. Plasma CL-K1 levels were weakly correlated with prothrombin time, activated partial thromboplastin time, and antithrombin levels; plasma MBL levels were weakly correlated with fibrin/fibrinogen degradation product levels and DIC score. In conclusion, during the first 5 days of ICU admission, plasma CL-K1 levels were similar between the DIC and non-DIC groups. However, plasma MBL levels were lower in the DIC group compared to the non-DIC group, and the significance of this difference grew gradually over time
Changes in Mannose-Binding Lectin and Collectin Kidney 1 Levels in Sepsis Patients With and Without Disseminated Intravascular Coagulation
補体系の役割と臨床医学でのトピックス
著者最終原稿版The complement has been identified as a complementation factor to compensate a function of antibody. The complement consists of C1-C9, complement related molecules, and its regulating molecules. Three major biological roles in complement are classified. First is an opsonization following the phagocytosis and elimination of microbes. Second is a direct destruction of bacteria due to make membrane attack complex (MAC). Third is a complement activation following the induction of anaphylactoid factors and local recruitment and activation of neutrophilic leukocytes. In this review, I summarize the basic findings and recent treatments of paroxysmal nocturnal hemogloburinuria (PNH) and hereditary angioedema (HAE). Finally, I make a short review with a rare autosomal recessive disorder of 3MC syndrome and propose the new biological functions of complement factors except for that of innate immunity
【消化管粘膜免疫の分子機構を探る 自然免疫と獲得免疫のクロストーク】 自然免疫においてMBLはどのような役割を果たすのか?
雑誌掲載版動物レクチンはカルシウム依存性レクチン(C型レクチン)と非依存性レクチンの2つに大別できる.コレクチンは内部構造にC型レクチンとコラーゲン様構造をもつ蛋白質の総称であり,その代表的な蛋白質としてマンナン結合レクチン(MBL)が知られている.MBLは,ヒトにおいてその遺伝子のSNPによる欠損症がおこり,そのために易感染性を呈する家系の存在が明らかになっている.そこで,in vitroの実験系と疫学的な研究により,最近明らかになった自然免疫にかかわるMBLの機能や役割について概説し
Additional Evidence for the Augmented Induction of Tumor-Specific Resistance in Vaccinia Virus-Primed Mice by Immunization with Vaccinia Virus-Modulated Syngeneic Tumor Cells
- …