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African Journal of Traditional,... 2017Beta-sitosterol (BS) is a compound discovered to be present in numerous plants. A number of interesting biomedical properties have been attributed to BS, including...
BACKGROUND
Beta-sitosterol (BS) is a compound discovered to be present in numerous plants. A number of interesting biomedical properties have been attributed to BS, including immuno-modulating and anti-inflammatory activities. Therefore, the aim of this report was to evaluate its anti-inflammatory capacity by applying various rodent experimental tests.
METHODS
To carry out the objective of the study we applied the methods indicated here. Two of the adopted methods were based on the passive reverse Arthus reaction: the rat paw edema test and the rat pleurisy assay. We also applied two methods related with the non-specific acute inflammation: the mouse ear edema test, and the mouse mieloperoxidase activity assay.
RESULTS
The results obtained in all tests established a significant anti-inflammatory potential of BS. In the rat paw edema test we found an inhibitory effect which goes from 50-70%; in the rat pleurisy assay our findings with respect to the volume of pleural exuded showed a reduction of 46%, as well as a 20% low amount of neutrophils in comparison with the level of the control group. In the mouse ear edema test we found a mean inflammatory inhibition of 75%, and with respect to mieloproxidase activity the results showed a significant inhibition induced by the three doses of BS.
CONCLUSIONS
In the present study we determined a potent anti-inflammatory capacity of BS in specific and non-specific types of acute inflammation in rodents.
Topics: Animals; Anti-Inflammatory Agents; Drug Evaluation, Preclinical; Edema; Humans; Male; Mice; Plant Extracts; Pleurisy; Rats; Rats, Wistar; Sitosterols
PubMed: 28480389
DOI: 10.21010/ajtcam.v14i1.13 -
The Journal of Experimental Medicine Jan 1908Following the divisions before used, the results presented in the preceding pages may be briefly stated. I. The particular method of sensitization and the place where...
Following the divisions before used, the results presented in the preceding pages may be briefly stated. I. The particular method of sensitization and the place where the test injection is made have an important bearing on the results obtained by various workers. Comparing the results obtained by the various methods, we may conclude that the incubation period of the hypersensitive reaction is not sharply limited, but that there is a progressive increase in sensitiveness from the sixth day, and presumably before that, extending over a period of several weeks. It seems very probable that the degree of hypersensitiveness attained where the sensitizing dose consists of a mixture of diphtheria toxin and serum is greater than when a single dose of the same small quantity of serum is given alone. II. Our early experiments, the first in this field, are in thorough agreement with those first reported by Otto, and shortly after him by Rosenau and Anderson. III. This hypersensitive reaction is transmissible from mother to offspring. The transmission is probably not equally effective in all cases, and individual young guinea-pigs probably vary greatly in the rate with which they lose their ability to react. As a result not all of the young of a hypersensitive mother react to a subcutaneous dose of five cubic centimeters of serum given when they are four or five weeks old. The reaction in the young animals differs quite markedly from that in those actively sensitized. These differences are such as to indicate that in the mother there is a considerable localization of the reaction in tissues and organs whose destruction does not cause sudden death. This local reaction is a protective factor and is not transmitted to the same degree as the factors involved in the fatal acute reaction. IV. The hypersensitive reaction to horse serum depends on the development of a special anti-body during the incubation period, which anti-body may be passively transferred to a fresh animal. If the dose of hypersensitive serum be sufficient, and the intoxicating injection be given directly into the circulation, this passive hypersensitiveness may be enough so that the animal will die when tested. There is also in the serum of hypersensitive guinea-pigs an uneliminated horse serum element or "rest," which is distinct from this antibody, and probably without influence on the course of the acute reaction. V. The anti-body on which the hypersensitive reaction depends may be entirely neutralized by horse serum without causing symptoms. The gradual introduction of increasing doses over a total period of twenty-four hours suffices for this. The animal is then, properly speaking, neither immune nor refractory, but is essentially in the condition of a normal animal which has recently had a large dose of horse serum. This rapid neutralization is made possible by the great binding power which the subcutaneous and other relatively unimportant tissues have for the toxic element of the serum. The so-called "Phenomenon of Arthus" is probably the same reaction for the rabbit that we have here dealt with in the guinea-pig. The fact that the manifestation is more prominently a local one depends on racial differences. I have encountered cases in the guinea-pig in which the conditions in the rabbit are closely simulated.
PubMed: 19867119
DOI: 10.1084/jem.10.1.1 -
Thorax May 1968A further example of diffuse pulmonary hypersensitivity to an inhaled organic antigen is reported. A 42-year-old maltworker, who developed an illness resembling farmer's...
A further example of diffuse pulmonary hypersensitivity to an inhaled organic antigen is reported. A 42-year-old maltworker, who developed an illness resembling farmer's lung, was found to have been heavily exposed to the spores of Precipitating and complement-fixing antibodies against an extract of were detected in his serum, a late (Arthus-type) reaction was produced by intradermal injection of the same extract, and a pyrexial reaction, accompanied by a reduction in forced vital capacity and carbon monoxide transfer factor, occurred 6 hours after the inhalation of spores of Two of the patient's four workmates complained of similar but less severe symptoms, and their sera also contained specific antibodies. Although the spores of and of , the fungus responsible for maple-bark disease, are much larger than the 1 μ spores of sp., they may give rise to a diffuse pulmonary hypersensitivity reaction indistinguishable from that observed in farmer's lung. This suggests that the occurrence of such a reaction is not necessarily related to the size of the inhaled particles, and there is reason to believe that the concentration of spores or other antigenic particles in the inspired air may in this respect be more important than their size. The pulmonary hypersensitivity in this group of disorders appears to be a precipitin-mediated (type III) response to a variety of inhaled antigens, but some of these antigens may in certain patients, presumably atopic individuals, also provoke a reagin-mediated (type I) bronchial hypersensitivity reaction. It is suggested that a term such as `allergic alveolitis' or `extrinsic allergic alveolitis' may suitably be used to describe the group of diseases caused by pulmonary hypersensitivity to inhaled organic antigens.
Topics: Adult; Antigen-Antibody Reactions; Aspergillus; Body Temperature; Complement Fixation Tests; Humans; Immunodiffusion; Lung Diseases, Fungal; Male; Occupational Diseases; Pneumonia; Pulmonary Alveoli; Respiratory Function Tests; Respiratory Hypersensitivity; Spores
PubMed: 4968543
DOI: 10.1136/thx.23.3.271 -
Arthritis & Rheumatology (Hoboken, N.J.) Nov 2018Immune complex (IC) deposition activates polymorphonuclear neutrophils (PMNs), increases vascular permeability, and leads to organ damage in systemic lupus erythematosus...
OBJECTIVE
Immune complex (IC) deposition activates polymorphonuclear neutrophils (PMNs), increases vascular permeability, and leads to organ damage in systemic lupus erythematosus and rheumatoid arthritis. The bioactive lipid sphingosine 1-phosphate (S1P), acting via S1P receptor 1 (S1P ), is a key regulator of endothelial cell (EC) barrier function. This study was undertaken to investigate whether augmenting EC integrity via S1P signaling attenuates inflammatory injury mediated by ICs.
METHODS
In vitro barrier function was assessed in human umbilical vein endothelial cells (HUVECs) by electrical cell-substrate impedance sensing. Phosphorylation of myosin light chain 2 (p-MLC-2) and VE-cadherin staining in HUVECs were assessed by immunofluorescence. A reverse Arthus reaction (RAR) was induced in the skin and lungs of mice with S1P deleted from ECs (S1P EC-knockout [ECKO] mice) and mice treated with S1P agonists and antagonists.
RESULTS
S1P agonists prevented loss of barrier function in HUVECs treated with IC-activated PMNs. S1P ECKO and wild-type (WT) mice treated with S1P antagonists had amplified RAR, whereas specific S1P agonists attenuated skin and lung RAR in WT mice. ApoM-Fc, a novel S1P chaperone, mitigated EC cell barrier dysfunction induced by activated PMNs in vitro and attenuated lung RAR. Expression levels of p-MLC-2 and disruption of VE-cadherin, each representing manifestations of cell contraction and destabilization of adherens junctions, respectively, that were induced by activated PMNs, were markedly reduced by treatment with S1P agonists and ApoM-Fc.
CONCLUSION
Our findings indicate that S1P signaling in ECs modulates vascular responses to IC deposition. S1P agonists and ApoM-Fc enhance the EC barrier, limit leukocyte escape from capillaries, and provide protection against inflammatory injury. The S1P/S1P axis is a newly identified target to attenuate tissue responses to IC deposition and mitigate end-organ damage.
Topics: Adherens Junctions; Anilides; Animals; Antigen-Antibody Complex; Antigens, CD; Apolipoproteins M; Arthus Reaction; Cadherins; Capillary Permeability; Cardiac Myosins; Endothelial Cells; Human Umbilical Vein Endothelial Cells; Humans; Indans; Lung; Lysophospholipids; Mice; Mice, Knockout; Myosin Light Chains; Organophosphonates; Oxadiazoles; Receptors, Lysosphingolipid; Skin; Sphingosine; Sphingosine-1-Phosphate Receptors; Thiophenes
PubMed: 29781582
DOI: 10.1002/art.40558 -
Blood May 2008The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others;...
The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding-observed mostly from venules-occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (alphaIIbbeta3, glycoprotein Ibalpha [GPIbalpha], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CalDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia.
Topics: Animals; Blood Platelets; Capillary Permeability; Hemorrhage; Inflammation; Mice; Platelet Adhesiveness; Thrombocytopenia
PubMed: 18256319
DOI: 10.1182/blood-2007-11-123620 -
Stem Cell Research & Therapy Jun 2019Mounting evidence has shown that a novel subset of mesenchymal stem cells (MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells (GMSCs)...
BACKGROUND
Mounting evidence has shown that a novel subset of mesenchymal stem cells (MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells (GMSCs) displays a greater immunotherapeutic potential and regenerative repair expression than MSCs obtained from other tissues. However, the safety of the use of transplanted GMSCs in humans remains unclear.
METHODS
In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagle dog, and monkey as well as two animal models of autoimmune diseases.
RESULTS
In short- and long-term toxicity tests, infused GMSCs had no remarkable adverse effects on hematologic and biochemical indexes, particularly on the major organs such as heart, liver, spleen, and kidney in recipient animals. It was also shown that GMSCs were well tolerated in other assays including hemolysis, vascular, and muscular stimulation, as well as systemic anaphylaxis and passive skin Arthus reaction in animal models. GSMC infusion did not cause any notable side effects on animal models of either autoimmune arthritis or lupus. Significantly, GMSCs most likely play no role in genotoxicity and tumorigenesis. The biological features remained stable for an extended period after cell transfer.
CONCLUSIONS
GMSCs are safe in various animal models of autoimmunity, even during active disease episodes, especially in monkeys. This study paves a solid road for future clinical trials of GMSCs in patients with autoimmune and inflammatory diseases.
Topics: Anaphylaxis; Animals; Arthritis; Autoimmunity; Cell Differentiation; Dogs; Female; Gingiva; Haplorhini; Humans; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Rabbits; Rats
PubMed: 31196163
DOI: 10.1186/s13287-019-1262-5 -
Immunology Jan 1964A technique for elicitation of simultaneous passive cutaneous anaphylaxis and reverse passive Arthus reactions in the same animal is described. Experimental evidence is...
A technique for elicitation of simultaneous passive cutaneous anaphylaxis and reverse passive Arthus reactions in the same animal is described. Experimental evidence is presented to substantiate previous findings that these two skin reactions, inducible by the same BSA-rabbit anti-BSA system, are distinctive in several species. Dose—response data on Arthus and PCA reactions in the mouse, rat, and guinea-pig indicated that the mouse was least sensitive and guinea-pig most sensitive to these cutaneous reactions. Both types of cutaneous reactions were found to decrease in intensity as well as diameter in response to excess antigen in all three species.
Topics: Allergy and Immunology; Animals; Antigen-Antibody Reactions; Arthus Reaction; Cattle; Guinea Pigs; Hypersensitivity; Mice; Passive Cutaneous Anaphylaxis; Rats; Research; Serum Albumin; Serum Albumin, Bovine; Skin Tests
PubMed: 14113080
DOI: No ID Found -
Infection and Immunity Feb 2006Staphylococcal protein A (SpA) is representative of a new class of antigens, the B-cell superantigens (SAgs). These antigens bind to the Fab regions of immunoglobulin...
Staphylococcal protein A (SpA) is representative of a new class of antigens, the B-cell superantigens (SAgs). These antigens bind to the Fab regions of immunoglobulin molecules outside their complementarity-determining regions. SpA, the best-studied B-cell SAg, reacts with the Fabs of most VH3+ immunoglobulins, which are expressed on 30 to 60% of human peripheral B cells. Therefore, B-cell SAgs like SpA have great potential to elicit inflammatory responses in vivo. We previously reported that the interaction of SpA with VH3+ immunoglobulin molecules leads to activation of the complement cascade and produces a histologic pattern of inflammation in the skin of a rabbit indicative of immune complex injury. To elucidate the cellular and molecular events contributing to this type of unconventional immune complex-mediated inflammation, we established a mouse peritoneal Arthus reaction model. Mice treated intravenously with human polyclonal immunoglobulin G (IgG), followed by intraperitoneal injection of SpA, showed neutrophil influx into the peritoneal cavity with peak numbers appearing at 8 h. This inflammatory reaction was dependent on the interaction of SpA with VH3+ IgG. Mast cells, FcgammaRIII, complement components, and tumor necrosis factor alpha play obligatory roles, and the reaction is associated with the local release of the CXC chemokines macrophage inflammatory protein 2 and KC. The data provide further compelling evidence for the induction of immune complex-mediated injury by a B-cell SAg and highlight important factors contributing to the pathogenesis of this novel type of inflammatory reaction.
Topics: Animals; Arthus Reaction; B-Lymphocytes; Female; Humans; Immunoglobulin G; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Peritoneal Cavity; Staphylococcal Protein A; Superantigens
PubMed: 16428769
DOI: 10.1128/IAI.74.2.1196-1203.2006 -
British Journal of Pharmacology Jan 19941. The role of the adhesion glycoproteins CD18 and intercellular adhesion molecule-1 (ICAM-1) in inflammatory responses produced during a reversed passive Arthus (RPA)...
1. The role of the adhesion glycoproteins CD18 and intercellular adhesion molecule-1 (ICAM-1) in inflammatory responses produced during a reversed passive Arthus (RPA) reaction and induced by zymosan and zymosan-activated plasma (ZAP) were studied in rabbit skin. 2. Oedema formation and haemorrhage were quantified by measuring accumulation of 125I-albumin and 111In-labelled red blood cells (111In-RBC) respectively. 3. Monoclonal antibody (mAb) R15.7 (anti-CD18), administered intravenously, abolished accumulation of 125I-albumin and 111In-RBC in dermal RPA reactions and in response to locally injected zymosan and ZAP. 4. When administered intravenously, the mAb RR1/1 (anti-ICAM-1) suppressed 125I-albumin and 111In-RBC accumulation in dermal RPA reactions and at sites treated with zymosan and ZAP. 5. Oedema formation in response to platelet-activating factor (PAF) and bradykinin (BK) either in the presence or absence of prostaglandin E2 (PGE2) were not affected by mAb R15.7 or by mAb RR1/1.1.1. 6. We conclude that oedema formation and haemorrhage associated with RPA reactions and in responses to zymosan and ZAP are completely CD18-dependent, and are mediated, at least in part, via ICAM-1. Responses to the neutrophil-independent oedema forming mediators, PAF and BK are not dependent upon CD18 or ICAM-1.
Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Arthus Reaction; Bradykinin; CD18 Antigens; Cell Adhesion Molecules; Dinoprostone; Dogs; Edema; Hemorrhage; Humans; Intercellular Adhesion Molecule-1; Mice; Platelet Activating Factor; Rabbits; Receptors, Leukocyte-Adhesion; Skin; Zymosan
PubMed: 7912151
DOI: 10.1111/j.1476-5381.1994.tb14032.x -
P-selectin requirement for neutrophil accumulation and injury in the direct passive Arthus reaction.Clinical and Experimental Immunology May 1998The aim of this study was to investigate the role of P-selectin in the accumulation of neutrophils in the direct passive Arthus reaction in rat skin. Direct passive...
The aim of this study was to investigate the role of P-selectin in the accumulation of neutrophils in the direct passive Arthus reaction in rat skin. Direct passive Arthus dermal reaction was induced in male Sprague-Dawley (SD) rats by a single i.v. injection of rat anti-sheep globulin (SG) 1 h before i.d. injection of SG antigen. Anti-P-selectin or irrelevant control antibody was given 1 h before rat anti-SG injection. Complement depletion was also performed in a separate group by pretreatment with cobra venom factor (CVF). In all groups dermal swelling was assessed 4 h after antigen challenge. Four hours after antigen challenge, rats treated with control antibody developed skin swelling (2.29 +/- 0.47 mm), prominent complement deposition and neutrophil accumulation. This response was associated with local up-regulation of endothelial P-selectin. Pre-treatment with anti-P-selectin antibody 1 h before passive Arthus induction prevented skin swelling (0.29 +/- 0.06 mm, P < 0.05, cf with control antibody treatment), neutrophil accumulation and up-regulation of endothelial P-selectin despite complement deposition. CVF treatment prevented complement deposition, neutrophil accumulation and skin swelling (0.13 +/- 0.07 mm, P < 0.05, cf with saline treatment). However, endothelial P-selectin expression was still present. Inhibition of skin swelling and neutrophil accumulation in direct passive Arthus by functional inhibition of P-selectin suggest a pivotal role for this adhesion molecule in this inflammatory process. These results also suggest that multiple steps are involved in the evolution of direct passive Arthus, including both P-selectin expression and complement activation. However, while complement activation is essential for neutrophil accumulation and expression of dermal injury, P-selectin up-regulation initiated by antibody/antigen deposition occurs independently of complement activation.
Topics: Animals; Arthus Reaction; Complement Activation; Complement Inactivator Proteins; Elapid Venoms; Immunoenzyme Techniques; Male; Microscopy, Fluorescence; Neutrophils; P-Selectin; Rats; Rats, Sprague-Dawley; Up-Regulation
PubMed: 9649192
DOI: 10.1046/j.1365-2249.1998.00584.x