Crit Rev Immunol
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Lymphangioleiomyomatosis (LAM), a rare cystic lung disease with multi-organ involvement, occurs primarily in women of childbearing age. LAM can present sporadically or in association with tuberous sclerosis complex (TSC). Loss of lung function in patients with LAM can be attributed to the dysregulated growth of LAM cells, with dysfunctional TSC1 or TSC2 genes, which encode hamartin and tuberin, respectively, leading to hyperactivation of the mammalian target of rapamycin (mTOR). ⋯ Although many chemokines and their receptors could influence LAM cell mobilization, we propose that a positive-feedback loop is generated when dysfunctional TSC2 is present in LAM cells. We identified a group of chemokine receptors that is expressed in LAM cells and differs from those on smooth muscle and melanoma cells (Malme-3M). Chemokines have been implicated in tumor metastasis, and our data suggest a role for chemokines in LAM cell mobilization and thereby in the pathogenesis of LAM.
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The prostate is the target of many inflammatory and neoplastic disorders that affect men of all ages. Pathological conditions of the prostate gland range from infection of this organ by ascending bacteria from infected urine, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown etiology (accompanied with inflammation and lymphocyte infiltration of the gland), to benign hyperplasia and cancer. Patients under 50 years of age usually suffer from CP/CPPS, a chronic inflammatory syndrome characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction complaints. ⋯ It is anticipated that preclinical studies in experimental models for CP/CPSS will provide important insights into the etiopathogenic mechanisms involved in this disease. We discuss here the similarities and the differences between human disease and experimental models and argue for the importance of the prostate gland in male reproductive function. Ultimately, we suggest that a state of inflammation, originally incited by an autoimmune response within the prostate, together with a diminished prostate functionality, may compromise male fertility.
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The virulence of pathogenic bacteria is critically dependent on their ability to produce toxins that attack eukaryotic target cells. Microbial toxins are either structural components of the bacterial cell wall (endotoxins) or actively secreted proteins (exotoxins). Sepsis and septic shock, which represent major causes of mortality in modern intensive care medicine, are caused by an inadequate inflammatory and immunological host response to bacterial infection. ⋯ Furthermore, bacterial toxins targeting endothelial cells severely alter the behavior of extravascular cells and circulating leukocytes via excessive formation of vasoactive mediators and overexpression of adhesion molecules. Research on the effects of microbial toxins on vascular endothelium has broadened our general understanding of microbial strategies to induce organ damage, even in the absence of viable bacteria. Combining antitoxin strategies with antibiotic therapy may prove to be of benefit to patients suffering from bacterial sepsis in the future.
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Review
Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue.
Macrophages can metabolize arginine to nitric oxide in quantities that inhibit pathogens or nearby host cells. They can instead metabolize arginine to ornithine (a precursor of polyamines and collagen) in quantities that stimulate pathogens or nearby host cells. ⋯ Macrophages expressing these destructive or constructive phenotypes have been termed M-1 or M-2 because they also stimulate TH1 or TH2 responses, respectively. Factors that influence whether a macrophage expresses the M-1 or M-2 phenotype and the real or potential impact on immune responses and other host processes are discussed.
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IL-4 has been called the "prototypic immunoregulatory cytokine." Like many cytokines, it can affect a variety of target cells in multiple ways. IL-4 has an important role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-cell responses. It is produced only by a subset of activated hematopoietic cells, including T cells and Fc epsilon R1+ mast cells and basophils. ⋯ Recently, progress has been made in defining the T-cell- and Fc epsilon R1-receptor-mediated signals that stimulate IL-4 gene expression. These studies have demonstrated that there are common and cell-specific signaling pathways that regulate production of this cytokine. In this review, we summarize the activities of IL-4 defined both in vitro and in vivo and compare the signals leading to IL-4 expression in cells of both T- and mast-cell lineage.