The mast cell and its function in allergic disease

Holgate, Stephen T.

doi:10.1111/j.1365-2222.1991.tb01758.x

Cited by 32 publications

(15 citation statements)

References 50 publications

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“…The EAR begins almost immediately following exposure to allergen, reaches its peak at 15-20 min and is followed by resolution over the next 1-2 h. This process, involving the actions of histamine, prostaglandin D 2 and cysteinyl leukotrienes (LTC 4 , LTD 4 , LTE 4 ) is felt to be largely mast cell-dependent [35]. The LAR occurs 3-8 h after exposure to allergen and is associated with a marked influx of inflammatory cells (mast cells, eosinophils, neutrophils and lymphocytes) into the submucosa and epithelium [36].…”

Section: Discussionmentioning

confidence: 99%

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

Harbinson

MacLeod²,

Hawksworth³

et al. 1997

Eur Respir J

115

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Recent studies have suggested that theophylline, a nonspecific phospho-diesterase inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4 (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells. PDE4 inhibitors might, therefore, have beneficial effects in asthma. Sideeffects, specifically nausea, have limited the use of existing agents. CDP840 is an orally active, potent and selective PDE4 inhibitor. We have examined the effect of CDP840 on the allergen-induced asthmatic response, its possible modes of action, and its tolerability at therapeutic doses.A total of 54 patients were recruited to three double-blind, placebo-controlled studies. The first study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced asthmatic response in patients with known dual response to allergen. A second study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway responsiveness to histamine. A third study examined whether single dose CDP840 (15 and 30 mg) had significant bronchodilatory effects.In all studies, CDP840 was well-tolerated, with no patients reporting nausea. CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. The late asthmatic response (LAR) to allergen, expressed as area under the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which persisted to the end of the observation period. The early asthmatic response (EAR) was unaffected, and there was no bronchodilatory effect at the doses used. Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine.In conclusion, CDP840 significantly attenuated the late asthmatic response to allergen challenge in the absence of any bronchodilatory or histamine antagonist effect. This suggests that CDP840 may exert its effects via an anti-inflammatory mechanism.

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Section: Discussionmentioning

confidence: 99%

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

Harbinson

MacLeod²,

Hawksworth³

et al. 1997

Eur Respir J

115

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“…Mast cells have an important role not only in allergic reactions but also in a number of inflammatory processes [10][11][12]. These cells release several mediators which have neutrophil chemotactic activity, including LTB4 and che motactic cytokines [13,14].…”

Section: Introductionmentioning

confidence: 99%

Role of Resident Mast Cells and Macrophages in the Neutrophil Migration Induced by LTB<sub>4</sub>, fMLP and C5a des arg

Ribeiro

Souza-Filho²,

Souza³

et al. 1997

Int Arch Allergy Immunol

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In the present study, we have investigated the participation of resident peritoneal cells (macrophages and mast cells) in the neutrophil migration induced in rats by the intraperitoneal administration of LTB₄, fMLP or C5a des arg. The intraperitoneal injection of LTB₄ (10 nmol), fMLP (10 nmol) and C5a des arg (zymosan-activated plasma, 1 ml) caused an intense neutrophil migration compared to the saline control (1,000, 1,500 and 2,000%, respectively). An 83% depletion in the number of resident cells following peritoneal lavage reduced the LTB₄-stimulated neutrophil migration by 73.6% without affecting that caused by fMLP and C5a des arg. Increasing the peritoneal macrophage population (236%) by pretreating the cavities with thioglycollate enhanced the neutrophil migration induced by LTB₄ (129%), but did not alter that induced by fMLP and C5a des arg. Similarly, reducing the population of peritoneal mast cells containing toluidine-blue-staining granules by subchronically pretreating the cavities with compound 48/80 diminished the LTB₄-induced NM by 69% but had no effect on the responses to fMLP and C5a des arg. Pretreating the animals with dexamethasone strongly inhibited (70%) the neutrophil migration induced by the intraperitoneal injection of LTB₄, fMLP and C5a des arg. Indomethacin, BW A4C and NDGA had no such effect. The incubating medium from peritoneal macrophages and mast cells stimulated with LTB₄ induced neutrophil migration when injected into the peritoneal cavity of rats. This migration was strongly reduced (70%) by treating the cells with dexamethasone. In contrast, stimulating the cells with fMLP or C5a des arg did not result in the release of any promigratory activity into the incubating fluid. Our results suggest that LTB₄ induces neutrophil migration via a mechanism dependent on resident mast cells and macrophages while that induced by C5a des arg and fMLP seems to be independent of such cellular involvement. The neutrophil migration induced by LTB₄ is apparently mediated by factor(s) whose release is blocked by dexamethasone. fMLP and C5a appear to cause in vivo migration by the formation of a concentration gradient and by a glucocorticoid-sensitive mechanism different from that stimulated by LTB₄.

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“…These include the injection of polymyxin B [10], alum ad juvant [11], antigen-coated latex [12], parasitic larvae or ex tracts [13] and large volumes of physiological saline [14,15], In addition, several factors including LTB4, [16,17], C5a [18], PA F [19], IL-5 [20,21], IL-2 [22,23], IL-8 [24] and factors derived from mast cells [25,26], lymphocytes [27] and macrophages [28] are known to induce eosinophil mi gration in vivo and in vitro. However, the endogenous mediators responsible for eosinophil recruitment to the site o f inflammation have not yet been fully characterized.…”

Section: Introductionmentioning

confidence: 99%

Role of Resident Peritoneal Cells in Eosinophil Migration Induced by Saline

Oliveira

Faccioli²,

Cunha³

et al. 1994

Int Arch Allergy Immunol

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In the present study, we investigated the role of resident peritoneal cells as well as the mediators involved in the eosinophil migration induced by large volumes of physiological saline. Two consecutive intraperitoneal injections of saline given 48 h apart, induced a selective recruitment of eosinophils into the cavity. This response was not observed with phosphate-buffered saline (PBS). Saline-induced eosinophil migration may be mediated at least in part by LTB₄, since the lipoxygenase inhibitors BW A4C and MK 886 prevented the response. In the presence of saline, but not of PBS, mast cells and macrophages incubated in vitro released a factor which induced eosinophil migration when injected into the peritoneal cavity of rats. This release was inhibited by BW A4C and MK 886. These results indicate the importance of mast cells and macrophages in the eosinophil migration induced by saline and suggest the participation of LTB₄ in this phenomenon. An abrupt reduction in the extracellular potassium concentration at the membrane of resident cells may be responsible for the saline effects since addition of potassium ions to saline abolished the eosinophil chemotactic activity of the same as well as its ability to stimulate the release of eosinophil chemotactic factor in vitro. Dexamethasone blocked both the saline-induced eosinophil migration and the release of eosinophil chemotactic factor by mast cells and macrophages. Pretreatment of the animals with dexamethasone inhibited the eosinophil migration induced either by the supernatants of saline-stimulated mast cells and macrophages or by LTB₄. These results indicate that the release of additional mediators is necessary in order to account for the final eosinophil migration. This conclusion is supported by the observation that peritoneal cavities depleted of resident cells did not demonstrate eosinophil migration when challenged with either LTB₄ or the supernatants of saline-treated cells.

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The mast cell and its function in allergic disease

Cited by 32 publications

References 50 publications

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects

Role of Resident Mast Cells and Macrophages in the Neutrophil Migration Induced by LTB<sub>4</sub>, fMLP and C5a des arg

Role of Resident Peritoneal Cells in Eosinophil Migration Induced by Saline

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