The mast cell as a primary effector cell in the pathegenesis of asthma

Holgate, S T; Hardy, C. C.; Robinson, Clive; Agius, Raymond; Howarth, Peter H.

doi:10.1016/s0091-6749(86)80104-x

Cited by 104 publications

(47 citation statements)

References 72 publications

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“…Sequencing of 10 clones revealed the presence of two distinct cDNAs that we have named ␦I tryptase and ␦II tryptase (GenBank accession nos. AY055427 and AF206664, respectively 4 ). The ␦I tryptase cDNA sequence matched that predicted from the published partial sequence of the mMCP-7-like I gene, and the ␦II tryptase cDNA matched the published exonic sequence of the mMCP-7-like II gene (14).…”

Section: Cloning Of the ␦ Tryptase Cdnamentioning

confidence: 99%

“…Despite the underlying causes of these diseases not being fully understood, it is known that the number of mast cells is increased in the airways of patients with asthma (4) and in the synovial tissue of patients with rheumatoid arthritis (5)(6)(7). Although many of the products expressed by mast cells are capable of contributing to an inflammatory phenotype (4), it is becoming increasingly apparent that especially in asthma, tryptase is one of the most important (8 -10).…”

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confidence: 99%

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δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

Wang¹,

McNeil²,

Husain

et al. 2002

The Journal of Immunology

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Tryptases are neutral serine proteases selectively expressed in mast cells and have been implicated in the development of a number of inflammatory diseases including asthma. It has recently been established that the number of genes encoding human mast cell tryptases is much larger than originally believed, but it is not clear how many of these genes are expressed. A recent report suggested that the transcript for at least one of these genes, originally named mMCP-7-like tryptase, is not expressed. To further address this question, we screened tissue-specific RNA samples by RT-PCR, using primers designed to match the putative exonic sequence of this gene. We successfully generated and cloned the correctly sized RT-PCR product from mRNA isolated from the human mast cell-I cell line. Two distinct clones were identified whose nucleotide sequence matched the published sequence of the mMCP-7-like I and mMCP-7-like II genes. Transcripts were detected in a wide variety of human tissues including lung, heart, stomach, spleen, skin, and colon. A polyclonal antipeptide Ab that specifically recognizes the translated product of this transcript was used to demonstrate its expression in mast cells that reside in the colon, lung, and inflamed synovium. A recombinant form of this protein expressed in bacterial cells was able to cleave a synthetic trypsin-sensitive substrate, d-Ile-Phe-Lys pNA. These results suggest that the range of functional tryptases is larger than previously recognized. For simplicity, we suggest that the gene, transcripts, and corresponding protein product be named δ tryptase.

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Section: Cloning Of the ␦ Tryptase Cdnamentioning

confidence: 99%

mentioning

confidence: 99%

δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

Wang¹,

McNeil²,

Husain

et al. 2002

The Journal of Immunology

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show abstract

“…[6][7][8][9][10] IgE binds to basophils and mast cells through surface Fcε receptors, which when stimulated by antigen, cause the release of basophilic granules containing histamines and leukotrienes, that in turn stimulate the contraction of airway smooth muscle. [11][12][13] In asthma, IL-5 stimulates the production and maturation of eosinophils, which travel to the airways and release granular material, leading to mucus production and eventual airway remodeling in severe cases. [14] IL-13 shares some common activities with IL-4 through a common receptor, but has some non-redundant roles including being a major contributor to fibroblast stimulation and increased pulmonary fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of regulatory B cells increases allergic airway inflammation

et al. 2005

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Objective-To investigate the effect of the X-linked immunodeficiency (Xid) B cell defect on the response to the cockroach allergen in mice.Methods-Two cockroach allergen immunization and challenge protocols were employed to sensitize CBA/J wild-type and CBA/CaHN-btk(−/−)xid/J (Xid) mice. Blood and tissue samples were collected 24 and 48 hrs after the last intratracheal antigen challenge and were analyzed for several parameters of allergic inflammation.Results-Nearly equivalent amounts of serum IgE were detected in Xid and CBA/J mice after short-term antigen challenge despite the B cell deficiency in Xid mice. A decreased concentration of IgE was detected in CBA/J mice after repeated allergen challenges but not in the Xid mice. Correlating with the discrepancy in serum IgE levels, higher levels of IL-13, IL-5, IL-10 and CCL5 were measured in whole lung homogenates from allergen-challenged Xid mice compared to CBA/J mice. In addition, draining lymph node cells from Xid mice expressed elevated levels of IL-4, IL-5, IL-10 and IFNγ mRNA compared to cells from CBA/J mice after in vitro culture with cockroach antigen. An increase in lung inflammation, interstitial eosinophilia and mucus production was also observed in allergen-challenged Xid mice. CD95L expression increased on B-1a cells following allergen challenge, which was accompanied by an increase in lung CD4 + Th cell apoptosis in wild-type CBA/J mice. In contrast, Xid mice did not have an increase in CD4 + T cell apoptosis following allergen challenge.Conclusions-These data suggest a regulatory role for B-1a cells in reducing cytokine production, pulmonary inflammation, and CD4 + T cell survival during cockroach allergen-induced airway inflammation.

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“…IAR has been recognized as a consequence of IgE mast–cell–mediated immediate–type hypersensivity [75]. Since not only T cells but also mast cells have been reported to produce cytokines such as IL–3, GM–CSF and IL–5 almost as effectively as T cells [60, 61], several investigators consider that LAR may be a consequence of mast cell activation [63, 64, 65, 66].…”

Section: Role Of Mast Cells In the Pathogenesis Of Atopic Diseasesmentioning

confidence: 99%

Simple Understanding and Optimistic Strategy for Coping with Atopic Diseases

Okudaira

Mori²

1998

Int Arch Allergy Immunol

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In this article, accumulated investigations were reviewed to present an 'IL–5 central hypothesis' for eosinophilic inflammation. In this simple working hypothesis, mechanisms of clinical amelioration of atopic diseases manifested by glucocorticoids or immunosuppressants such as cyclosporin A or FK506 were easily understood to stem from the inhibition of IL–5 production and gene transcription. Screening of macrolide molecules resulted in the detection of nonactin (code name: OM–01), which inhibits production and gene transcription of IL–5 but not of IL–2 or IL–4. It was suggested that this kind of approach may open a new era of 'specific gene transcription control' for the management of allergic and other human disorders.

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The mast cell as a primary effector cell in the pathegenesis of asthma

Cited by 104 publications

References 72 publications

δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

Deficiency of regulatory B cells increases allergic airway inflammation

Simple Understanding and Optimistic Strategy for Coping with Atopic Diseases

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