H. Y. A. Lau

Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells.

BACKGROUND PentaHerbs formula (PHF) containing Cortex Moutan, root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera japonica Thunb. (Capri-foliaceae), Herba Menthae, aerial part of Mentha haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, rhizome of Atractylodes lancea (Thunb.) DC. (Compositae) at the ratio of 2:2:2:1:2 was useful in the management of eczema. AIM OF THE STUDY Since the mechanism of action of PHF is not known, we aimed to investigate the actions of PHF on mast cell activation. MATERIALS AND METHODS Effects of aqueous extracts of PHF and individual component herb on mediator release from rat peritoneal mast cells (RPMCs) and cytokine production from HMC-1 were investigated. RESULTS PHF, Cortex Moutan and Herba Menthae significantly attenuated histamine release and prostaglandin D(2) synthesis from RPMC activated by anti-IgE and compound 48/80 (p<0.05). While Flos Lonicerae and Rhizoma Atractylodis suppressed only mediator release from compound 48/80 activated RPMC, Cortex Phellodendri potentiated only anti-IgE induced mediator release (p<0.05). However, with the exception of Cortex Moutan, PHF and the other four component herbs failed to affect cytokine production in HMC-1. CONCLUSIONS Although individual herbs demonstrated different modulating effects on mast cells, inhibition of inflammatory mediator release from mast cells would contribute to the therapeutic efficacy of PHF.

Characterization of prostanoid receptors mediating inhibition of histamine release from anti-IgE-activated rat peritoneal mast cells

Prostanoid receptors mediating inhibition of anti‐IgE induced histamine release from rat peritoneal mast cells have been characterized pharmacologically. PGD2 and the specific DP receptor agonists BW 245C and ZK 118182 were the most potent inhibitors with half‐maximal concentrations of 0.26, 0.06 and 0.02 μM respectively. The maximum inhibition attainable was 60–65% with 10−5 M BW 245C and ZK 118182. Among several EP receptor agonists investigated, only PGE2 and the EP2/EP3 receptor agonist misoprostol induced significant inhibition (46.8±4.7% at 10−4 M and 18.7±6.8% at 10−5 M respectively). The IP receptor agonists cicaprost and iloprost were both less potent than the DP agonists in inhibiting histamine release (45.2±3.3% and 35.1±2.5% inhibition respectively at 10−5 M), whereas PGF2α and the TP receptor agonist U‐46619 were only marginally effective. The EP4/TP receptor antagonist AH 23848 failed to affect the inhibitory actions of PGD2 or PGE2 even at 10−5 M, whereas the DP/EP1/EP2 receptor antagonist AH 6809 slightly enhanced the effect of PGD2 at 10−6 M. At concentrations of 3×10−6 to 10−5 M, the putative DP receptor antagonist ZK 138357 dose‐dependently suppressed the inhibitory activities of the DP agonists, PGE2 and cicaprost. The antagonism of ZK 138357 against the DP receptor agonists appeared to be competitive with pA2 values of around six. In conclusion, these data support our earlier proposal that an inhibitory DP receptor is the predominant prostanoid receptor in rat peritoneal mast cell. The properties of this receptor in relation to putative DP receptor subtypes reported in the literature are discussed.

Prostaglandin E2 potentiates the immunologically stimulated histamine release from human peripheral blood-derived mast cells through EP1/EP3 receptors

Background:  Mast cells cultured from human peripheral blood have been widely used to study human mast cell function. Prostanoids are the important regulators of mast cell activity, however, there were no reports about the class of prostanoid receptors expressed on such cultured cells.

PGE2 suppresses excessive anti-IgE induced cysteinyl leucotrienes production in mast cells of patients with aspirin exacerbated respiratory disease

Background:  Aspirin causes bronchospasm in patients with aspirin exacerbated respiratory disease (AERD). The contribution of mast cells to the increased cysteinyl‐leucotrienes (cys‐LTs) detected in AERD patients is however not defined.

Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models

Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross‐linking of allergen‐specific IgE‐bound high‐affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi‐synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti‐malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti‐allergic effects of artesunate in animal models of IgE‐dependent anaphylaxis.

Effects of Long-Acting β2-Adrenoceptor Agonists on Mast Cells of Rat, Guinea Pig, and Human

The effects of two recently developed long-acting beta 2-adrenoceptor agonists, formoterol and salmeterol, on mast cells from different sources were compared with those of the prototype short-acting analogue, salbutamol. With the exception of high concentrations of salmeterol (> 10(-5) M), none of the tested beta 2-adrenoceptor agonists inhibited the anti-IgE-induced histamine release from rat peritoneal mast cells. In contrast, all three compounds dose dependently inhibited the immunologically induced histamine release from isolated lung mast cells of guinea pig and human at concentrations < or = 10(-5) M.

Induction of nitric oxide synthases in primary human cultured mast cells by IgE and proinflammatory cytokines

The mast cells have been suggested to be a cellular source of nitric oxide (NO) which level is increased in the pathogenesis of asthma. However, isoforms of the NO generating enzyme, nitric oxide synthase (NOS), in primary human mast cells have not been defined due to the lack of a suitable model. We hence examined directly the expression of NOS mRNA and proteins in primary human cultured mast cells (HCMC). Mature HCMC were cultured from CD34+ progenitors isolated from buffy coat preparations and were subjected to IgE sensitisation, IgE receptor mediated activation and cytokines induced stimulation. While expression of NOS mRNA was detected by conventional reverse transcription-polymerase chain reaction (RT-PCR) and quantitatively analyzed with real-time RT-PCR, expression of NOS proteins was detected by immunostaining. In non-stimulated HCMC incubated in medium alone, expressions of NOS were not detected. While overnight incubation of HCMC with IgE significantly increased the expression of NOS2 and NOS3, only NOS2 expression was up-regulated after overnight incubation with a mixture of TNF-alpha, IFN-gamma and IL-1beta. Cross-linking of IgE with anti-IgE further increased NOS2 expression with a concomitant decrease in NOS3 expression. NOS1 was not detected in all treatments. In conclusion, we have shown for the first time that NOS2 and NOS3 expressions are induced in primary human mast cells following appropriate stimulations. Comparisons between the differential expressions of NOS isoforms in HCMC to the changes in NOS expressions in asthma models suggest that the mast cell is a source of NO in asthmatic airways.

EFFECTS OF BETA 2-ADRENERGIC AGONISTS ON ISOLATED GUINEA PIG LUNG MAST CELLS

The mast cell protective effects of the newly developed long-actingβ2-adrenergic salmeterol and formoterol were compared with those of conventionally usedβ2-adrenergic, non-specific β-agonists, disodium cromoglycate (DSCG) and theophylline. With the exception of DSCG, all the test agents inhibited ovalbumin-induced histamine release from enzymically dispersed guinea pig lung mast cells in a dose-dependent fashion. At the maximum concentration tested, theophylline produced the highest level of protection, inhibiting up to 90% of ovalbumin-induced histamine release whereas DSCG produced only 10% inhibition. The maximum inhibition produced by all theβ2-adrenergic tested was around 45%. While salmeterol was equipotent with salbutamol, formoterol was at least a 100-fold more potent. Hence the present study confirmed the previously reported mast cell stabilizing actions of conventionalβ2-adrenergic and extended the observation to the newly developed long-acting analogues.

Suppression of mast cell activity contributes to the osteoprotective effect of an herbal formula containing Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae

Mast cells are believed to contribute to the pathogenesis of osteoporosis as their number is increased in osteoporotic bones. Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three Chinese herbs traditionally for tonifying the ‘kidney system’ and a herbal formula (ELP) containing the respective herbs at the weight ratio of 5 : 4 : 1 was shown to prevent osteoporosis. This study evaluated if suppression of mast cell accumulation and activity contribute to the anti‐osteoporotic action of ELP.

Adenosine: roles of different receptor subtypes in mediating histamine release from human and rodent mast cells.

Adenosine, an endogenous nucleoside, exertsmodulating effects in many cellular systems. Four distinct subtypes of adenosine receptors (A1, A2A, A2B and A3) belonging to the G-protein-coupled receptor family have been classified according to their ability to regulate adenylate cyclase activity [1]. Adenosine can provoke bronchoconstriction when inhaled by asthmatic individuals but not in normal subjects [2] indirectly through mast cells [3]. While a predominantly excitatory action of adenosine on mast cell activation was confirmed in rodents, less conclusive results were obtained in humans [4, 5]. The aim of our study is to compare the effects of adenosine and adenosine receptor agonists on basal and anti-IgE induced histamine release from rat and human mast cells.