Methionine sulfoxide reductases protect against oxidative stress in Staphylococcus aureus encountering exogenous oxidants and human neutrophils.

To establish infection successfully, Staphylococcus aureus must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence on the fate of S. aureus exposed to oxidants or PMN.

agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils.

The emergence of serious infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has fueled interest in the contributions of specific staphylococcal virulence factors to clinical disease. To assess the contributions of agr-dependent factors to the fate of organisms in polymorphonuclear neutrophils (PMN), we examined the consequences for organism and host cells of feeding PMN with wild-type CA-MRSA (LAC) or CA-MRSA (LAC agr KO) at different multiplicities of infection (MOIs). Phagocytosed organisms rapidly increased the transcription of RNAIII in a time- and MOI-dependent fashion; extracellular USA300 (LAC) did not increase RNAIII expression despite having the capacity to respond to autoinducing peptide-enriched culture medium.

The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma.

Background: A disintegrin and metalloprotease (ADAM)-33 is a susceptibility gene for asthma and chronic obstructive pulmonary disease whose function remains unknown.

Objective: Because asthmatic bronchoalveolar lavage fluid contains high levels of soluble ADAM33 (sADAM33), which includes the catalytic domain, we postulated that its release from cell membranes might play functional roles in airway remodeling by promoting angiogenesis.

Methods: The proangiogenic activity of the highly purified catalytic domain of ADAM33 or a catalytically inactive mutant was studied in vitro (Matrigel assay), ex vivo (human embryonic/fetal lung explants) and in vivo (chorioallantoic membrane assay).

The genetics of asthma: ADAM33 as an example of a susceptibility gene.

The ability to identify novel disease genes by positional cloning led to the identification of a disintegrin and metalloprotease (ADAM)33 gene on chromosome 20p13 as a susceptibility gene for asthma. Case-control and family-based association studies have mostly confirmed a link between ADAM33 and asthma. Its restricted expression to mesenchymal cells as well as its association with bronchial hyperresponsiveness and accelerated decline in lung function over time point strongly to its involvement in the structural airway components of asthma, such as remodeling.

Degenerate self-reactive human T-cell receptor causes spontaneous autoimmune disease in mice.

Thyroid autoimmune disorders comprise more than 30% of all organ-specific autoimmune diseases and are characterized by autoantibodies and infiltrating T cells. The pathologic role of infiltrating T cells is not well defined. To address this issue, we generated transgenic mice expressing a human T-cell receptor derived from the thyroid-infiltrating T cell of a patient with thyroiditis and specific for a cryptic thyroid-peroxidase epitope.