Structure and distribution of alpha-1-microglobulin proteins

Detta är en avhandling från Department of Cellular and Molecular Biology. Sölvegatan 39 22100 Lund

Sammanfattning: This thesis describes studies of the structure and tissue distribution of alpha-1-microglobulin (a1-m), a member of the lipocalin protein superfamily with immunosuppressive properies. It was shown that a1-m appears in human plasma in five major forms. These were identified as monomeric a1-m and covalent complexes between a1-m and IgA, prothrombin, albumin and a1-m. In addition to blood, both monomeric-, and high molecular weight forms of a1-m were present in tissues. The liver, kidney and heart contained a series of a1-m isoforms with apparent molecular masses between 40 kDa and 50 kDa, which were not present in plasma. Immunohistochemical analysis of human tissue demonstrated intracellular labeling of a1-m in hepatocytes and in the proximal epithelial cells of the kidney. In addition, a1-m immunoreactivity was detected in the interstitial connective tissue of heart, lung and in the adventitia of blood vessels as well as on cell surfaces of cardiocytes. a1-m mRNA was detected only in the liver and pancreas. This suggests that the protein found in other tissues is not synthesized locally, but transported to the tissues via the bloodstream from the production sites in liver and pancreas. a1-m was found in placenta particularly at sites of syncytiotrophoblast injury. Thus, ?tissue a1-m? may act as a local immunosuppressive barrier in the placenta, protecting the chorionic villi from the immune system of the mother. a1-m is yellow-brown. Colored tryptic peptides of a1-m were purified, and it was shown that the side chains of Lys92, Lys118 and Lys130 in these peptides carried size heterogeneous covalently attached groups with molecular masses beetween 106 and 282 Da. The fluorescence properties and molecular modeling suggested that the chromophores were most likely buried and closely spaced in the interior of the protein. Only the free a1m carried colored groups, whereas the a1m linked to IgA was uncolored.

  Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.