PCR was employed to determine the presence of all known superantigen genes (sea, seq, and tst) and of the exotoxin-like gene cluster (set) in 40 Staphylococcus aureus isolates from blood cultures and throat swabs; 28 isolates harbored superantigen genes, five on average, and this strictly correlated with their ability to stimulate T-cell proliferation. In contrast, the set gene cluster was detected in every S. aureus strain, suggesting a nonredundant function for these genes which is different from T-cell activation. No more than 10% of normal human serum samples inhibited the T-cell stimulation elicited by egc-encoded enterotoxins (staphylococcal enterotoxins G, I, M, N, and O), whereas between 32 and 86% neutralized the classical superantigens. Similarly, intravenous human immunoglobulin G preparations inhibited egc-encoded superantigens with 10-to 100-fold-reduced potency compared with the classical enterotoxins. Thus, there are surprisingly large gaps in the capacity of human serum samples to neutralize S. aureus superantigens.Staphylococcus aureus persists as a commensal microorganism in 10 to 30% of the population, but the organism is also a common cause of food poisoning and infections of different severity such as skin abscesses and wound infections, osteomyelitis, endocarditis, pneumonia, toxic shock syndrome, and staphylococcal scarlet fever (21). S. aureus is one of the most frequent causes of hospital-acquired infections, and the emergence and spread of multiresistant strains give rise to concern. The pathogenicity of S. aureus is multifactorial, and the versatility of this organism is underscored by recent clinical studies (4,14,16,31,37,38).Superantigens activate large subpopulations of T lymphocytes by directly cross-linking certain T-cell receptor V domains with conserved structures on major histocompatibility complex class II molecules (32). They belong to the most potent T-cell mitogens known and can induce massive systemic cytokine release, leading to the symptoms of toxic shock syndrome (22). Among the virulence factors of S. aureus are the staphylococcal enterotoxins, the causative agents of food poisoning. They also act as superantigens. Whole-genome sequencing of several S. aureus clinical isolates has revealed that all 17 known staphylococcal enterotoxins (staphylococcal enterotoxins A to E and G to Q and toxic shock syndrome toxin 1) are encoded on mobile genetic elements together with other virulence factors (3,18,40). For example, the recently described enterotoxin gene cluster egc, which contains the five superantigen genes seg, sei, sem, sen, and seo, as well as two pseudogenes is located on the genomic island SaPI3 (18).egc is special in that it functions as an operon and its genes are transcribed into a single polycistronic mRNA (13). In addition, a large cluster of up to 11 genes with sequence homology to superantigens has been discovered on the genomic island SaPI2; they have been termed staphylococcal exotoxinlike genes, or set (3,10,18,39). For an overview of the organization ...
FLT3 is a cytoprotective system in the heart and a potential therapeutic target in ischemic cardiac injury. The protective mechanisms uncovered here may be further explored in view of potential cardiotoxic effects of FLT3-targeting anticancer therapy, particularly in patients with ischemic heart disease.
The totality of functional cardiomyocytes and an intact cardiac progenitor cell pool are key players in the myocardial cell homeostasis. Perturbation of either one may compromise the structural and functional integrity of the heart and lead to heart failure. Reactive oxygen/nitrogen species (ROS/RNS) are important regulators of cardiomyocyte viability; more recently, the interrelation between ROS and progenitor cell behavior and fate has moved into the spotlight. Increasing evidence suggests not only that ROS participate in the regulation of cardiac progenitor cell survival but also that they likewise affect their functional properties in terms of self-proliferation and differentiation. The apparent dichotomy of ROS/RNS effects with their adaptive and regulatory character on the one hand and their maladaptive and damaging features on the other pose a great challenge in view of the therapeutic exploitation of their role in the regulation of the myocardial cell homeostasis. In this article, mechanisms and potential significance of ROS/RNS action in the regulation of the myocardial cell homeostasis, in particular with respect to the preservation of viable cardiomyocytes and the maintenance of a functional cardiac progenitor cell pool, will be discussed.
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