Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophil peroxidase (EPO) at relatively low levels (4-30 mU), when supplemented with H2O2 and a halide, induced mast cell degranulation. Histamine release occurred without concomitant release of the cytoplasmic marker lactic dehydrogenase (LDH), and this, together with ultrastructural studies, indicated a noncytotoxic effect comparable with that induced by other mast cell secretagogues. At pH 7.4, iodide was effective at concentrations down to 10(-5) M, and although chloride alone was ineffective at 0.1 M, a combination of 0.1 M chloride and 10(-6) iodide could meet the halide requirement. Chloride alone was effective at pH 6.5 and 6.0. EPO could be replaced by myeloperoxidase. When the EPO level was increased to 100 mU, combination with H2O2- and iodide-induced cytotoxic histamine release as indicated by concomitant LDH release and ultrastructural evidence of cell disruption. This cytotoxic response reverted to a secretory one on the addition of albumin. Peroxidase was detected on the surface of extruded granules by diaminobenzidine cytochemistry. The mast cell granule (MCG)/EPO complex when supplemented with H2O2 and iodide was more effective than free EPO in the stimulation of mast cell secretion. The stimulation of mast cell mediator release by the EPO-H2O2-halide system and the formation of MCG/EPO complexes with augmented cytotoxic activity may influence the adjacent inflammatory response.
 ...
PMID:Eosinophil peroxidase-induced mast cell secretion. 615 83

Heme-containing peroxidases have been demonstrated both biochemically and cytochemically in a variety of cells that either reside in the respiratory tract or circulate through it via the vasculature. The peroxidases in neutrophils and eosinophils have long been known to function in lung defense through their participation in an antimicrobial system involving hydrogen peroxide and chloride ions. Recent studies indicate that this system is also toxic to tumor cells and, as such, it may have a protective or mitigative effect on tumor formation in the lung. Eosinophil peroxidase may be involved in immediate hypersensitivity reactions in the lung because of its secretory effect on mast cells. Platelets contain peroxidases, but how they function is unknown. Whether peroxidase occurs in lymphocytes is controversial, but until more compelling evidence is presented they should be considered peroxidase-negative. A number of cells indigenous to the respiratory tract contain peroxidase activity, but there is considerable variability among species as to its presence and amount. When careful consideration is given to fixation and incubation conditions, peroxidase can be demonstrated cytochemically in the nuclear envelope and endoplasmic reticulum of some endothelial cells and type II cells of certain rodents, but its physiological role is speculative. The alveolar macrophages of most species possess little or no peroxidase activity apart from catalase which can function as a peroxidase under certain conditions. Mast cells in the respiratory tract contain peroxidase, but it is more easily demonstrated biochemically than cytochemically. The function of mast cell peroxidase is unknown, but two hypotheses worthy of investigation are its possible role in modulation of atopic allergic reactions and involvement in an antitumor defense mechanism similar to that of myeloperoxidase. Peroxidase is most abundant in the secretory cells of the tracheobronchial epithelium and glands where, in a number of species, it is synthesized and secreted as a component of mucus. Its possible contribution to lung defense is discussed in view of its morphologic similarity to the antibacterial peroxidase of milk and saliva. Because of the ease with which peroxidases can be demonstrated cytochemically, it is not surprising that morphologic information regarding their distribution in the respiratory tract has greatly exceeded insights into their functional significance. It is hoped that advancements in cell dissociation and culture, along with biochemical isolation and purification techniques, will lead to definitive conclusions concerning their physiologic roles in lung metabolism and defense.
 ...
PMID:The distribution and function of peroxidases in the respiratory tract. 638 50

Eosinophil peroxidase (EPO) and to a lesser degree neutrophil peroxidase (myeloperoxidase, MPO) bound tightly to mast cell granules (MCG), particularly when the latter were depleted of histamine by suspension in physiologic salt solutions. The bound EPO was localized on the surface of the granule, and its dissociation required salt concentrations of high enough ionic strength (greater than 0.75 M) to solubilize the MCG matrix. Elution of MPO from the complex occurred at a lower salt concentration. The MCG/EPO complex retained the capacity of the isolated EPO to catalyze the iodination reaction when supplemented with iodide, H2O2, and a protein acceptor and to kill microorganisms when supplemented with H2O2 and a halide (iodide, chloride). Indeed, the MCG/EPO complex had significantly greater iodinating and bactericidal activity than the free enzyme when standardized to equal guaiacol units of peroxidase activity. Thus, in areas of inflammation where mast cells and phagocytic leukocytes coexist, there is the potential for the formation of active complexes extracellularly between mast cell granules and molecules such as EPO (or MPO) that can affect the inflammatory response.
 ...
PMID:Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity. 698 10