Browsing by Subject "Chymase"

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    Mast cell chymase: an indispensable instrument in the pathological symphony of idiopathic pulmonary fibrosis?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Kosanovic, Djuro; Daha, Bhola Kumar; Wygrecka, Malgorzata; Reiss, Irwin; Günther, Andreas; Ghofrani, Ardeschir; Weissmann, , Norbert; Grimminger, Friedrich; Seeger, Werner; Schermuly, Ralph Theo; Banat, Gamal-Andre
    Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease with no known etiology and treatment options. The hallmarks of the histopathology, which is characteristic of usual interstitial pneumonia (UIP) pattern, include interstitial fibrosis, honeycomb changes and fibroblast foci that develop owing to fibroblast proliferation and excessive matrix deposition. Although the complete pathomechanism is not yet understood, several molecular culprits, including transforming growth factor (TGF)-ß, Angiotensin (Ang) II, endothelin (ET)-1, matrix metalloproteinases (MMPs) and cytokines have been identified. IPF is increasingly believed to be an epithelial-driven disease; however, the literature does support an implication of altered immune response and inflammatory processes in the onset or progression of the disease. Mast cells (MCs) are multifunctional tissue resident cells involved in the inflammatory and immune response. An increasing body of evidence suggests a role of MCs and their mediator chymase in the pathology of IPF. With regard to the underlying mechanisms, it is conceivable that MC chymase may function via activation or processing of factors such as proteases, cytokines and growth factors. In this review, we will discuss how MC chymase is linked to and can potentially contribute to the development of IPF. Moreover, the findings from animal model studies will be discussed to highlight the chymase inhibitors as a promising strategy for the treatment of pulmonary fibrosis.
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    Mast cell granule composition and tissue location - a close correlation
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Beil, W. J.; Schulz, M.; Wefelmeyer, U.
    This review provides a survey on mast cell heterogeneity, with aspects differing in humans and rodents or which are subject of conflicting evidence being discussed in greater detail. Mast cell subsets have been first defined in rats by their fixation and dyebinding properties, and detailed studies in humans and pigs reveal very similar observations. The dye-binding properties of rat mast cell subsets are causally related to the absence or presence of heparin in their granules. In humans, this relation has not been shown. Rodent mast cell subsets store different chymase-isoforms. In contrast, just a single chymase has been defined in humans, and mast cells are classified by the presence or relative absence of this chymase. Different investigators find quite different proportions of chymase-positive to chymase-negative mast cells. Tryptase(s) are found in most or every human mast cell, but in rodents, they have hitherto been essentially localised to mast cells in connective tissues. Human mast cell subsets may also be defined by their expression of receptors such as CSaR and possibly the B-chemokine receptor CCR3; the CCR3 expression seems to be related to the human mast cell chymase expression. Ultrastructural studies are helpful to distinguish human mast cell subsets, and allow to distinguish between chronic and acute activation. The phenotypical characteristics may change in association with inflammation or other disease processes. Studies in humans and pigs show changed dye-binding and fixation properties of the granules. Experimental rodent infection models reveal similar changes of chymase isoform expression. Human lung mast cells have been reported to strongly upregulate their chymase content in pulmonary vascular disease. This line of evidence can explain some inconsistent information on mast cell heterogeneity and may help to understand the physiological role of mast cells.