scholarly journals TISSUE MAST CELLS AND ACUTE INFLAMMATION IN EXPERIMENTAL CUTANEOUS MUCORMYCOSIS OF NORMAL, 48/80-TREATED, AND DIABETIC RATS

1960 ◽  
Vol 112 (6) ◽  
pp. 1069-1084 ◽  
Author(s):  
Walter H. Sheldon ◽  
Heinz Bauer
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Response ◽  
Alloxan Diabetes ◽  
Acute Inflammation ◽  
Normal Function ◽  
Tissue Mast Cell ◽  
Cytoplasmic Granules ◽  
Cutaneous Mucormycosis ◽  
Fungus Growth

The role of the tissue mast cells in relation to the acute inflammatory reaction to experimental cutaneous mucormycosis was studied histologically in normal rats, in animals whose tissue mast cells had been depleted of their cytoplasmic granules prior to infection by the administration of compound 48/80 and in others in whom acute alloxan diabetes with acidosis had been produced before injection of the fungus. The discharge of the tissue mast cell granules in normal rats occurred within minutes at the site of infection and appeared to initiate the rapid onset of acute inflammation. The degranulation of the tissue mast cells subsided in a short time and the cells reassumed a normal histologic appearance while inflammation progressed with the formation of circumscribed lesions. In animals pretreated with compound 48/80 in which the tissue mast cells contained no granules, the onset of inflammation was briefly delayed, the intensity of the process was somewhat decreased, fibroblastic proliferation was retarded, and the fungus growth in the early lesions was increased. However, the infection did not spread and the lesions were well localized. The tissue mast cells in the diabetic and acidotic rats completely failed to discharge their cytoplasmic granules, the onset and intensity of the acute inflammatory response were markedly delayed and decreased and the infection progressed rapidly with massive fungus growth invading adjacent tissues. A relationship between the discharged tissue mast cell granules and eosinophilic granulocytes was noted since the latter were numerous among the inflammatory cell exudate in normal rats and scarce in the lesions of the diabetic animals. It is concluded that a function of the tissue mast cells in the normal rat is the rapid initiation of acute inflammation at the site of injury and that degranulation of these cells prior to infection somewhat delays the inflammatory response and therefore slightly diminishes host resistance. Furthermore, a severe metabolic disorder such as acute alloxan diabetes with acidosis, inhibits the normal function of the tissue mast cells, delays and decreases inflammation, and in this manner contributes to the greatly increased susceptibility of the host to infection.

scholarly journals Mast Cell Chymase and Kidney Disease

2020 ◽  
Vol 22 (1) ◽  
pp. 302
Author(s):  
Shamila Vibhushan ◽  
Manuela Bratti ◽  
Juan Eduardo Montero-Hernández ◽  
Alaa El Ghoneimi ◽  
Marc Benhamou ◽  
...  
Keyword(s):  
Mast Cell ◽  
Angiotensin Ii ◽  
Mast Cells ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Inflammatory Mediator ◽  
Total Proteins ◽  
Cytoplasmic Granules ◽  
Physiological Processes ◽  
Mast Cell Chymase

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.

scholarly journals THE DEVELOPMENT OF THE ACUTE INFLAMMATORY RESPONSE TO EXPERIMENTAL CUTANEOUS MUCORMYCOSIS IN NORMAL AND DIABETIC RABBITS

1959 ◽  
Vol 110 (6) ◽  
pp. 845-852 ◽  
Author(s):  
Walter H. Sheldon ◽  
Heinz Bauer
Keyword(s):  
Inflammatory Response ◽  
Polymorphonuclear Leukocytes ◽  
Mononuclear Cells ◽  
Acute Inflammatory Response ◽  
Cutaneous Mucormycosis ◽  
Resistance To Infection ◽  
Diabetic Rabbits ◽  
Host Metabolism ◽  
Histologic Changes ◽  
Fungus Growth

The histologic changes associated with the development of the acute inflammatory response to experimental cutaneous mucormycosis were studied at various times from 5 minutes to 24 hours after inoculation into normal rabbits and in rabbits with acute alloxan diabetes and acidosis. In normal animals the response by polymorphonuclear leukocytes began within a few minutes after inoculation, increased rapidly in extent and intensity and reached its peak within 6 to 12 hours. By that time there was also early proliferation of fibroblasts and of large mononuclear cells and these cellular reactions, together with the accumulated granulocytes, began to produce a demarcation of the lesions. Beginning 4 to 6 hours after inoculation the fungus showed some growth but this remained confined to the necrotic center of the lesions. In the diabetic rabbits the onset of the response by polymorphonuclear leukocytes was delayed by several hours, reduced in intensity and was apparently less effective. There was no proliferation of fibroblasts and the lesions were spreading rather than circumscribed. Fungus growth in the tissues began shortly after inoculation, was marked, progressed rapidly, and soon extended beyond the site of inoculation. The large mononuclear cells, however, appeared at about the same time and in equal number in the lesions of both diabetic and non-diabetic animals and showed no morphologic changes. It is concluded that a significant delay and impaired effectiveness of the response by polymorphonuclear leukocytes, a lack of fibroblastic proliferation and an enhanced growth of the fungus lower host resistance to infection with it and are directly consequent on severe alterations in host metabolism.

scholarly journals CHANGES IN SECRETION OF RAT SKIN MAST CELLS IN SYSTEMIC INFLAMMATORY RESPONSE

2020 ◽  
Vol 10 (2) ◽  
pp. 61-68
Author(s):  
N. V. Yaglova ◽  
S. S. Obernikhin ◽  
V. V. Yaglov
Keyword(s):  
Immune Response ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Response ◽  
Systemic Inflammatory Response ◽  
Sublethal Dose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Rat Skin ◽  
Functional Changes

Mast cells are active participants of innate immune response. Systemic immune response induces functional changes even in organs, which are not considered primary targets of bacterial or viral infections. Cytophysiology of mast cells located in organs not affected by systemic inflammatory response, like skin, is still poorly studied. Investiga- tions of this issue might elucidate some pathogenetic mechanism of skin diseases associated with previously devel- oped intestinal or respiratory infection. The aim was to investigate structural changes of rat skin mast cells in systemic inflammatory response indicative of mast cell secretion. Materials and methods: The experiment was performed on 45 male Wistar rats. Systemic inflammatory response was induced by intraperitoneal injection of sublethal dose of lipopolysaccharide E. coli (20mg/kg). The survived rats were sacrificed 1 and 7 days after injection. Serum levels of interleucine-2, 12p40, and interferon-γ were evaluated by enzyme-linked immunosorbent assay. Histological examination of abdominal skin slices, stained with hematoxilin and eosin and toluidine blue was performed. Results. The rats developed systemic inflammatory response, which attenuated on the 7th day after lipopolysac- charide injection. No significant changes in skin morphology were found. Skin mast cells demonstrated some morpho- logical and functional changes indicative of active secretion of mediators without activation of degranulation. On the 7th day mast cell cytophysiology had no significant changes compared to the control group. Conclusion. Systemic inflammatory response induced by bacterial lipopolysaccharide does not activate migration of mast cells to skin, but changes their secretory processes by enhancing peace-meal degranulation.

scholarly journals Mast Cells and Basophils in the Defense against Ectoparasites: Efficient Degradation of Parasite Anticoagulants by the Connective Tissue Mast Cell Chymases

2021 ◽  
Vol 22 (23) ◽  
pp. 12627
Author(s):  
Zhirong Fu ◽  
Srinivas Akula ◽  
Anna-Karin Olsson ◽  
Jukka Kervinen ◽  
Lars Hellman
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Blood Feeding ◽  
Cathepsin G ◽  
Human Mast Cell ◽  
Mucosal Mast Cell ◽  
Tissue Mast Cell ◽  
Tick Feeding

Ticks, lice, flees, mosquitos, leeches and vampire bats need to prevent the host’s blood coagulation during their feeding process. This is primarily achieved by injecting potent anticoagulant proteins. Basophils frequently accumulate at the site of tick feeding. However, this occurs only after the second encounter with the parasite involving an adaptive immune response and IgE. To study the potential role of basophils and mast cells in the defense against ticks and other ectoparasites, we produced anticoagulant proteins from three blood-feeding animals; tick, mosquito, and leech. We tested these anticoagulant proteins for their sensitivity to inactivation by a panel of hematopoietic serine proteases. The majority of the connective tissue mast cell proteases tested, originating from humans, dogs, rats, hamsters, and opossums, efficiently cleaved these anticoagulant proteins. Interestingly, the mucosal mast cell proteases that contain closely similar cleavage specificity, had little effect on these anticoagulant proteins. Ticks have been shown to produce serpins, serine protease inhibitors, upon a blood meal that efficiently inhibit the human mast cell chymase and cathepsin G, indicating that ticks have developed a strategy to inactivate these proteases. We show here that one of these tick serpins (IRS-2) shows broad activity against the majority of the mast cell chymotryptic enzymes and the neutrophil proteases from human to opossum. However, it had no effect on the mast cell tryptases or the basophil specific protease mMCP-8. The production of anticoagulants, proteases and anti-proteases by the parasite and the host presents a fascinating example of an arms race between the blood-feeding animals and the mammalian immune system with an apparent and potent role of the connective tissue mast cell chymases in the host defense.

An improved method for staining mouse mast cells

1989 ◽  
Vol 67 (1) ◽  
pp. 226-227 ◽  
Author(s):  
M. Novak ◽  
S. Nombrado
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Alcian Blue ◽  
Cell Types ◽  
Mucosal Mast Cell ◽  
Improved Method ◽  
Tissue Mast Cell ◽  
Pathological Conditions

An improved method for staining mouse mast cells with alcian blue is reported. The reaction differentiates between mucosal mast cell and connective tissue mast cell types, especially under pathological conditions.

Reduction of ethanol-induced gastric damage by sodium cromoglycate and FPL-52694. Role of leukotrienes, prostaglandins, and mast cells in the protective mechanism

1989 ◽  
Vol 67 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Paul L. Beck ◽  
Gerald P. Morris ◽  
John L. Wallace
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Connective Tissue ◽  
Sodium Cromoglycate ◽  
Mechanism Of Action ◽  
Gastric Damage ◽  
Gastric Mucosal Damage ◽  
Tissue Mast Cell ◽  
Cell Numbers ◽  
Two Agents

The mechanism of action of the "mast cell stabilizers" sodium cromoglycate and FPL-52694 as protective agents against ethanol-induced gastric mucosal damage was investigated in the rat. Using an ex vivo gastric chamber model, various concentrations (10–80 mg/mL) of the two agents were applied to the gastric mucosa prior to exposure to 40% ethanol. Both agents significantly reduced ethanol-induced damage in a dose-dependent manner. When given orally (80 mg/kg) both agents significantly reduced gastric damage induced by subsequent oral administration of absolute ethanol. Pretreatment with indomethacin did not significantly affect the protection afforded by FPL-52694, but did cause a partial reversal of the protective effect of sodium cromoglycate. Changes in gastric leukotriene C4 synthesis did not correlate with the protective effects of the two agents. Both mucosal and connective tissue mast cell numbers were significantly reduced following oral ethanol administration. In the groups pretreated with FPL-52694 or sodium cromoglycate, mucosal mast cell numbers were not significantly different from those in rats not treated with ethanol. Furthermore, the connective tissue mast cell numbers were significantly lower than in ethanol-treated control rats, despite a >95% reduction of ethanol-induced hemorrhagic damage. These results therefore suggest that stimulation of gastric prostaglandin synthesis is not important in the mechanism of action of FPL-52694, and neither agent appears to reduce damage through a mechanism related to effects on gastric leukotriene C4 synthesis. The present studies further suggest that the protection afforded by pretreatment with sodium cromoglycate or FPL-52694 may be unrelated to effects of these agents on the connective tissue mast cell population in the stomach.Key words: ulcer, eicosanoids, mast cells, alcohol, mast cell stabilizers.

Mast cells mediate the microvascular inflammatory response to systemic hypoxia

2003 ◽  
Vol 94 (1) ◽  
pp. 325-334 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Response ◽  
Vascular Permeability ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Leukocyte Adherence ◽  
Systemic Hypoxia

Systemic hypoxia produces an inflammatory response characterized by increases in reactive O2 species (ROS), venular leukocyte-endothelial adherence and emigration, and vascular permeability. Inflammation is typically initiated by mediators released from activated perivascular cells that generate the chemotactic gradient responsible for extravascular leukocyte accumulation. These experiments were directed to study the possible participation of mast cells in hypoxia-induced microvascular inflammation. Mast cell degranulation, ROS levels, leukocyte adherence and emigration, and vascular permeability were studied in the mesenteric microcirculation by using intravital microscopy of anesthetized rats. The main findings were 1) activation of mast cells with compound 48/80 in normoxia produced microvascular effects similar, but not identical, to those of hypoxia; 2) systemic hypoxia resulted in rapid mast cell degranulation; 3) blockade of mast cell degranulation with cromolyn prevented or attenuated the hypoxia-induced increases in ROS, leukocyte adherence/emigration, and vascular permeability; and 4) mast cell degranulation during hypoxia was prevented by administration of the antioxidant lipoic acid and of nitric oxide. These results show that mast cells play a key role in hypoxia-induced inflammation and suggest that alterations in the ROS-nitric oxide balance may be involved in mast cell activation during hypoxia.

scholarly journals Ultrastructural localization of basic proteins in cytoplasmic granules of rat eosinophils and mast cells.

1980 ◽  
Vol 28 (3) ◽  
pp. 238-244 ◽  
Author(s):  
P F Pimenta ◽  
M A Loures ◽  
W de Souza
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Basic Protein ◽  
Ultrastructural Localization ◽  
Ultrastructural Level ◽  
Cytoplasmic Granules ◽  
Basic Proteins ◽  
Intense Reaction ◽  
The Matrix ◽  
Ammoniacal Silver

The postformalin ammoniacal silver (AS) and the ethanolic phosphotungstic acid (EPTA) methods were used to localize basic protein at the ultrastructural level in cytoplasmic granules of rat eosinophils and mast cells isolated using a Metrizamide gradient. Intense reaction was seen in the granules of EPTA-treated eosinophils. Following incubation of the cells for 2 hr in EPTA alone, the matrix was stained. After longer incubation (10 hr), however, both the matrix and core were stained. Cytoplasmic granules of the mast cell show a slight or negative reaction with EPTA. With the AS technique, a large number of silver particles were seen in the nucleus of both eosinophils and mast cells. The mast cell cytoplasmic granules showed intense reaction, while those from eosinophils showed no clear reaction. Acetylation of the cells under conditions sufficient to block most free amino groups prio to EPTA or AS treatment greatly reduced (EPTA) or abolished (AS) the reaction. The results indicate 1) that eosinophil granules contain basic proteins both in the matrix and the core, 2) that the mast cell granules contain a basic protein (probably the alpha-chymotrypsin-like enzyme), which reacts strongly with AS, and 3) that the AS and EPTA methods have different specificities.

scholarly journals Effects of Toxin A from Clostridium difficile on Mast Cell Activation and Survival

1998 ◽  
Vol 66 (6) ◽  
pp. 2755-2761 ◽  
Author(s):  
Gloria M. Calderón ◽  
Javier Torres-López ◽  
Tong-Jun Lin ◽  
Bibiana Chavez ◽  
Manuel Hernández ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Clostridium Difficile ◽  
Inflammatory Response ◽  
Inflammatory Mediators ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Toxin A ◽  
Tnf Α ◽  
Vitro Effect

ABSTRACT Toxins A and B from Clostridium difficile are the main cause of antibiotic-associated diarrhea and pseudomembranous colitis. They cause fluid accumulation, necrosis, and a strong inflammatory response when inoculated in intestinal loops. Since mast cells are a rich source of inflammatory mediators, abundant in the gut, and known to be involved in C. difficile-induced enteritis, we studied the in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as a model of antigen-independent activation, and PMC from sensitized rats were stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast cell activation. After 4 h, toxin A did not induce release of nitric oxide or histamine in naive PMC. However, 10 ng of toxin per ml caused a significant release of tumor necrosis factor alpha (TNF-α). In contrast, 1 μg of toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin A at 1 μg/ml for 4 h caused disruption of actin which aggregated in the cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was documented also. These results suggest that mast cells may participate in the initial inflammatory response toC. difficile infection by releasing TNF-α upon interaction with toxin A. However, longer exposure to toxin A affects the release of inflammatory mediators, perhaps because of the alteration of the cytoskeleton and induction of apoptosis. The impaired functions and survival of mast cells by C. difficile toxin A could hamper the capacity of these cells to counteract the infection, thus prolonging the pathogenic effects of C. difficiletoxins.

scholarly journals Comparative Analysis Of Orthologous Mast Cell Chymases Active Sites Using Bioinformatics Tools

2021 ◽  
Author(s):  
Jawairia Kiran
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Active Site ◽  
Active Sites ◽  
Cytotoxic T Cells ◽  
Residue Analysis ◽  
Catalytic Triad ◽  
Cytoplasmic Granules ◽  
Human Sequence ◽  
Binding Residues

Abstract Mast cells, neutrophils, basophils, natural killer cells, and cytotoxic T cells are among the hematopoietic cell lines originating from immune cells. The importance of mammalian mast cells in innate immunity has piqued the scientific community's interest. cytoplasmic granules of mast cells. Histamine, proteoglycans, proteins, and cytokines are examples of compounds (mediators) that produce mast cell cytoplasmic granules. When external stimuli are received, these granules are released, causing degranulation. Mast cells generate a lot of proteases including chymase, tryptase, and type A carboxypeptidase, among other things. The structure of chymase cma1 was unknown in mice, but it shares 74 percent of its human sequence with chymase CMA1, which was used as a reference. The human CMA1 structure was used to establish and interpret the mouse cma1 structure. Significant residues from the active site, such as catalytic triads and binding residues, were examined. The position of a catalytic triad in human CMA1 chymase and mouse cma1 chymase has been discovered to be similar. Val 175 and Val 197, respectively, replaced two Ala 192 and Gly 214 residues in active site binding residues in target, according to active site residue analysis. We may deduce from this substitution that the cleavage specificity of mouse cma1 chymase varies from that of human CMA1 chymase.

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