L'asthme est une maladie inflammatoire des voies aériennes dans laquelle différentes cellules et éléments cellulaires interagissent. L'asthme provoque des épisodes d'oppression thoracique et de toux, en particulier la nuit ou au petit matin. Ces épisodes sont généralement associés à une obstruction réversible des voies aériennes soit spontanément soit sous l'effet d'un traitement. Les principales caractéristiques de l'asthme sont une hyperréactivité bronchique, une inflammation à prédominance éosinophiles ainsi qu'un remodelage des bronches. Toutes ces caractéristiques structurelles suggèrent un rôle pour différentes protéases et notamment celles de la familles des adamlysines. En effet, les ADAM et ADAMTS protéases sont caractérisées par les domaines disintégrine et métalloprotéase qui leur confèrent les propriétés des molécules d'adhésion et des protéases. Dans ce travail, nous avons étudié ces protéases potentiellement intéressantes dans l'asthme.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 189-242). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 189-242). Also available on the Internet.

No description available.

The complement system is considered as the chief recognition and effector component of innate immunity; it is involved in inflammation and enhances the adaptive immune response. Factor I (fI) is a heterodimeric serine protease consisting of a heavy (HC) and a light-catalytic (LC) chain; it circulates in an active form regulating complement by selectively cleaving only C3b or C4b in the presence of a cofactor such as factor H (fH), CR1, MCP or C4bp. The cleavage of C3b occurs through a ternary complex formed between fI, C3b and a cofactor like fH and yields iC3b, a major opsonin. The structural and functional properties of fI were investigated. The interchain disulphide bond formed between C³⁰⁹-C⁴³⁵ tnat links the HC and LC of fI as well as the composition of the TV-linked carbohydrates of fI were determined. By using two independent assays, the proteolytic and amidolytic assays, the catalytic properties of human fI were characterised in detail. The catalytic subunit, the SP domain, was shown to have a native conformation that accommodates substrate recognition and cleavage, fI has specificity similar to thrombin, but exhibits lower catalytic activity. fI amidolytic activity reaches optimum at pH 8.25 and is insensitive to ionic strength. This is in contrast to its proteolytic activity within the fI-C3b-fH reaction, in which the pH optimum for C3b cleavage is <5.5 and the reaction rate is highly dependent on ionic strength. The rate of cleavage of tripeptide AMC substrates by fI was unaffected by fH or C3(NH₃) at optimum pH. fI and the isolated SP domain were found to have similar amidolytic activities, but strikingly different proteolytic activities on C3(NH 3 ). fl did not cleave C3(NH₃) in the absence of fH, but cleaved it rapidly at two sites in its presence. The SP domain however, cleaved C3(NH₃) slowly in the absence of fH, at more than two sites. Cleavage by the SP domain was inhibited, not stimulated, by fH. These results suggested that the HC domains and/or the cofactor must orient the natural substrates and restrict cleavage by fI to the two sites which yield iC3b. The implications of these findings are discussed.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Includes bibliographical references (leaves 102-135) Also available in print.

Thesis (Ph.D.)--Baylor University, 2008. / Includes bibliographical references (p. 296-303).

Dissertation (Ph.D.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2004. / Dr. Suzanne Shuker, Committee Member ; Dr. Niren Murthy, Committee Member ; Dr. Donald Doyle, Committee Member ; Dr. Nicholas Hud, Committee Member ; Dr. James C. Powers, Committee Chair. Includes bibliographical references.

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.