title: Heparan Sulfate Proteoglycan Metabolism and the Fate of Grafted Tissues.
abstract: Tissue and organ transplants between genetically distinct individuals are always or nearly always rejected. The universality and speed of transplant rejection distinguishes this immune response from all others. Although this distinction is incompletely understood, some efforts to shed light on transplant rejection have revealed broader insights, including a relationship between activation of complement in grafted tissues, the metabolism of heparan sulfate proteoglycan and the nature of immune and inflammatory responses that ensue. Complement activation on cell surfaces, especially on endothelial cell surfaces, causes the shedding heparan sulfate, an acidic saccharide, from the cell surface and neighboring extracellular matrix. Solubilized in this way, heparan sulfate can activate leukocytes via toll like receptor-4, triggering inflammatory responses and activating dendritic cells, which migrate to regional lymphoid organs where they spark and to some extent govern cellular immune responses. In this way local ischemia, tissue injury and infection, exert systemic impact on immunity. Whether or in what circumstances this series of events explains the distinct characteristics of the immune response to transplants is still unclear but the events offer insight into the inception of immunity under the sub-optimal conditions accompanying infection and mechanisms by which infection and tissue injury engender systemic inflammation.
authors: Transplantation Biology, Department of Surgery, University of Michigan, A520B Medical Sciences Research Building I, 1150W. Medical Center Drive, Ann Arbor, MI, 48109-5656, USA, plattjl@umich.edu.
authors: Jeffrey L
authors: JL
authors: Platt
authors: Lucile E
authors: LE
authors: Wrenshall
authors: Geoffrey B
authors: GB
authors: Johnson
authors: Marilia
authors: M
authors: Cascalho
mesh_terms: D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000187:drug effects / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism*; D006497:Heparan Sulfate / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016378:Tissue Transplantation; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D003165:Complement System Proteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D051197:Toll-Like Receptor 4; C495345:TLR4 protein, human