Inflammation in rats born to mothers treated with dexamethasone 15cH during pregnancy: an immunohistochemical study

In previous studies, we observed that rats born to mothers treated with dexamethasone 15CH (10-33M) had a higher level of mast cell degranulation and greater arteriolar dilation after the exposure of an inflammatory stimulus, suggesting the possibility of vertical transmission of the effects of ultra-diluted substances between mother and offspring. In this study, a more detailed assessment of the cellular events in acute inflammation was made using techniques of immunohistochemistry. The identification of adhesion molecules expression was made by the markers: anti-CD54 (ICAM-1) and anti-CD18 (β2-Integrin). The identification of inflammatory cells was performed by the markers anti-MAC387 (mononuclear cells) and anti-CD163 (active macrophages). Polymorphonuclear cells were identified by hematoxylin-eosin staining. The number of labeled cells per field was recorded, except for the anti-CD54 marker, whose intensity of staining on the endothelial cells was defined by scores assigned by two independent observers. The results point toward to an up regulation of the whole inflammatory process in rats born to mothers treated with dexamethasone 15CH during pregnancy. This conclusion is justified by the following statistically significant (p≤0.05) findings: a) bigger mast cell degranulation and increased of arteriolar diameter; b) increased migration of polymorphonuclear cells in relation to the mononuclear cells; c) earlier expression of CD163 in monocytes, d) higher level of adhesion molecules expression.

The effect of local passive heating on skeletal muscle histamine concentration: Implications for exercise-induced histamine release

Aerobic exercise induces mast cell degranulation and increases histamine formation by histidine decarboxylase, resulting in an ~150% increase in intramuscular histamine. The purpose of this study was to determine if the increase in skeletal muscle temperature associated with exercise is sufficient to explain this histamine response. Specifically, we hypothesized that local passive heating that mimics the magnitude and time-course of changes in skeletal muscle temperature observed during exercise would result in increased intramuscular histamine concentrations comparable to exercising values. Seven subjects participated in the main study in which pulsed short-wave diathermy was used to passively raise the temperature of the vastus lateralis over 60 min. Heating increased intramuscular temperature from 32.6 (95% CI 32.0 to 33.2) to 38.9 (38.7 to 39.2) oC (P < 0.05) and increased intramuscular histamine concentration from 2.14 (1.92 to 2.36) to 2.97 (2.57 to 3.36) ng/ml (P < 0.05), an increase of 41%. In a follow-up in vitro experiment utilizing human-derived cultured mast cells, heating to comparable temperatures did not activate mast cell degranulation. Therefore, it appears that exercise-associated changes in skeletal muscle temperature are sufficient to generate elevations in intramuscular histamine concentration. However, this thermal effect is most likely due to changes in de novo histamine formation via histidine decarboxylase and not due to degranulation of mast cells. In conclusion, physiologically relevant increases in skeletal muscle temperature explain part, but not all, of the histamine response to aerobic exercise. This thermal effect may be important in generating the positive adaptations to exercise training.

Mast Cell Stabilizing, Antianaphylactic and Bronchodilatory activity of Methanolic extract of Averrhoa carambola Fruit

This work was mainly aimed to study the mast cell stabilizing, anti-anaphylactic and bronchodilatory activities of methanolic extract of Averrhoa carambola (ACME). Mast cell stabilization activity was investigated by Compound 48/80 induced mast cell degranulation in rats and antianaphylactic activity was performed by determining the mortality rate of mice upon exposure to compound 48/80. The bronchodilatory effect of ACME was studied on histamine aerosol-induced bronchospasm using guinea pigs, in which occurrence of preconvulsive dyspnea (PCD) was noted as end point. Treatment with ACME (100, 200 and 400mg/kg) showed significant (p<0.05) protection of rat peritoneal mast cells and significantly (p<0.05) reduced the mortality of mice in a dose dependent manner. ACME significantly (p<0.05) increased the time of preconvulsive dyspnea (PCD) in a dose dependent manner that suggestive of bronchodilating activity. Phytochemical studies observed presence of saponins, tannins, steroids, alkaloids, flavonoids and glycosides. From these finding, we concluded that ACME possesses mast cell stabilizing; anti anaphylactic and bronchodilatory activity which might be used in treatment of asthma.

Dimerized Translationally Controlled Tumor Protein-Binding Peptide 2 Attenuates Systemic Anaphylactic Reactions Through Direct Suppression of Mast Cell Degranulation

Dimerized translationally controlled tumor protein (dTCTP) amplifies allergic responses through activation of several types of immune cells and release of inflammatory mediators. In particular, dTCTP plays an important role in histamine release by triggering mast cells and has been proposed as a target in the treatment of allergic diseases. dTCTP-binding peptide 2 (dTBP2) is known to attenuate severe allergic rhinitis and asthma through inhibition of dTCTP activity on airway epithelial cells and T cells; however, it is unclear whether dTBP2 affects mast cell function and mast cell disease. In this study, we explored the effects of dTBP2 on mast cell degranulation and allergen-induced anaphylactic reactions. We found that bacterial product lipopolysaccharide increased the expression of dTCTP in mast cells and rapidly released dTCTP by the mast cell stimulator compound 48/80. Interestingly, the released dTCTP further promoted mast cell degranulation in an autocrine activation manner and increased calcium mobilization in mast cells, which is essential for degranulation. Furthermore, dTBP2 directly and dose-dependently inhibited in vitro mast cell degranulation enhanced by compound 48/80, suggesting a direct and potent anti-anaphylactic activity of dTBP2. dTBP2 also significantly suppressed the dTCTP-induced degranulation and histamine release through inhibition of the p38 MAPK signaling pathway and suppression of lysosomal expansion and calcium mobilization in mast cells. More importantly, in vivo administration of dTBP2 decreased mortality and significantly attenuated histamine release and inflammatory cytokine production in compound 48/80-induced systemic anaphylactic reactions. These results suggest that dTBP2 is beneficial for the control of anaphylaxis with increased dTCTP.