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Innate Cellular Lectin-Mediated Binding of Xenogeneic Antigens

先天细胞凝集素介导的异种抗原结合

基本信息

批准号：
7681659
负责人：
MICHAEL A REES
金额：
$ 24.27万
依托单位：
UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-09 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7681659
关键词：
Acids Acute Liver Failure Animal Organ Animals Annexin A1 Annexin A4 Annexins Antigens Binding Blood Carbohydrates Cell Line Cell Surface Proteins Cell Surface Receptors Cell surface Cells Chinese Hamster Climacteric Cloning Data Development Erythrocytes Family suidae Genetic Engineering Glycopeptides Glycophorin A Hepatic Heterophile Antigens Human Immune Investigation Kupffer Cells Lectin Lectin Receptors Ligands Liver Mediating Mind Modeling Molecular Monosaccharides N-Acetylneuraminic Acid Oligosaccharides Organ Organ Transplantation Ovarian Patients Perfusion Phenotype Play Pre-Clinical Model Primates Process Proteins Research Personnel Role Sialic Acids Source Technology Testing Thinking Time Transplantation Work Xenograft procedure clinically relevant design improved functioning insight liver function macrophage meetings prevent receptor success sugar tool

项目摘要

DESCRIPTION (provided by applicant): Organ transplantation has changed the lives of hundreds of thousands of patients. In fact, it is the success of transplantation that has led to its major limitation-there simply are not enough organs to meet the demand. Thus, researchers are looking for alternative sources of organs for transplantation. A strategy thought likely to succeed is the use of animal organs to replace failed human organs, a process known as xenotransplantation. Recent developments in genetic engineering and cloning technology have raised hopes that xenotransplantation will become a successful treatment within the next few decades. The pig is the animal felt to be the most appropriate source of organs in this regard. Extracorporeal liver perfusion (ECLP) has been suggested as one of the first applications of a vascularized porcine organ for the treatment of a patient. ECLP is felt to be a reasonable first choice because patients in fulminant liver failure have a lifethreatening condition and do not have alternative temporary means of support. In addition, ECLP could be used before long-term survival of vascularized organs has been achieved in a primate model as ECLP has been shown to provide hepatic support over a short period of time that is well within the current expected survival of vascularized porcine organs in primates. One of the barriers preventing the application of ECLP is the loss of erythrocytes that occurs when human blood perfuses a porcine liver. Further investigation has demonstrated that porcine Kupffer cells are responsible for the destruction of the human erythrocytes by a mechanism involving Kupffer cell surface protein receptor recognition of foreign human sugar molecules. Such sugar recognizing proteins are called lectins. Sialic acid has been identified as a component of the carbohydrate ligand being recognized and porcine annexins I, II and IV have been identified as potential lectin receptors responsible for the binding. Specific aims 1 and 2 propose to identify the exact sugars being recognized and to evaluate the role of porcine annexins as the receptor responsible for binding human erythrocytes. Specific aim 3 proposes to use this new information to design a substance that will prevent the loss of human erythrocytes during liver xenoperfusion and to test this substance in a pre-clinical model of extracorporeal porcine liver perfusion. This work will advance our understanding of macrophage recognition of foreign sugars from other species and make ECLP a more useful tool in treating fulminant hepatic failure.

描述（由申请人提供）：