No description available.

No description available.

No description available.

Techn. University, Diss., 2005--München.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Umeå Universitet, Sweden, 1991. / Extra t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1971. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 100-104).

The little studied plasma kallikrein-kinin system of poikilotherm vertebrates was investigated in several species offish, amphibians, and reptiles, and compared to the well-known mammalian enzyme system. It was found that the plasmas of all fish and amphibians tested differed from reptilian and mammalian plasma in their inability to release a kinin-like factor when reacted with trypsin or glass, and no evidence was obtained to suggest that these plasmas contain enzymic machinery which can produce a kinin. However, it was shown that heat-denatured plasma from these animals did develop biological activity when treated with hog pancreas kallikrein, an enzyme specific for releasing kinins. Thus, the equivalent of a kininogen might exist in these plasmas. Since turtle plasma produced a kinin by endogenous enzymes, detailed studies of this system were conducted. By a variety of criteria, enzymic mechanisms for kinin production in this plasma were closely similar to those of mammalian plasma. However, purification of the turtle kinin released by endogenous enzymes, followed by pharmacological and chemical tests showed that this kinin was chemically different from bradykinin, its mammalian counterpart. Data obtained from amino acid analysis of the peptide, and from certain pharmacological tests, strongly suggested that the structure of turtle kininis 6-thr-bradykinin; i.e., that a threonine residue has been substituted for a serine . The possible significance of this finding is discussed. Preliminary studies of the pharmacological effects of bradykinin on aspects of blood pressure and flow in the turtle itself are described. Intra-arterial injections of bradykinin over a wide range of doses always produced a press or response which could be greatly reduced by adrenergic blockade. This is in contrast with the effect of, the peptide in mammals, where there is typically a hypotensive response which cannot be reduced by adrenergic blockade. The significance of this difference is discussed, and approaches to future investigations are suggested. / Science, Faculty of / Zoology, Department of / Graduate

Ferritin is a protein principally known for its role in iron storage. We have previously shown that ferritin can bind high-molecular-weight kininogen (HK). Upon proteolytic cleavage by the protease kallikrein, HK releases the proinflammatory peptide bradykinin (BK) and other biologically active products, such as two-chain high-molecular-weight kininogen, HKa. At inflammatory sites, HK is oxidized, which renders it a poor substrate for kallikrein. However, oxidized HK remains a good substrate for elastase and tryptase, thereby providing an alternative cleavage mechanism for HK during inflammation. Here we report that ferritin can retard the cleavage of both native HK and oxidized HK by elastase and tryptase. Initial rates of cleavage were reduced 45-75% in the presence of ferritin. Ferritin is not a substrate for elastase or tryptase and does not interfere with the ability of either protease to digest a synthetic substrate, suggesting that ferritin may impede HK cleavage through direct interaction with HK. Immunoprecipitation and solid phase binding studies reveal that ferritin and HK bind directly with a Kd of 134 nM. To test whether ferritin regulates HK cleavage in vivo, we used THP-1 cells, a human monocyte/macrophage cell line that has been used to model pulmonary inflammatory cells. We observed that ferritin impedes the cleavage of HK by secretory proteases in stimulated macrophages. Furthermore, ferritin, HK, and elastase are all present in or on alveolar macrophages in a mouse model of pulmonary inflammation. Collectively, these results implicate ferritin in the modulation of HK cleavage at sites of inflammation.