Immunopathology and human mast cell cytokines

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Introduction

Mast cells originate from progenitor cells in the bone marrow, circulate as undifferentiated mononuclear cells in the peripheral circulation, and subsequently mature under local influences following migration into tissue. Mast cells are widely distributed throughout the body in both connective tissue and at mucosal surfaces, and it has been estimated that if all the mast cells in the body were assembled together, they might form an organ the size of the spleen. They form a heterogeneous population of cells with differences apparent in their development, mediator content, ultrastructure, and functionally in their ability to interact with their local environment [1]. It seems likely therefore that human mast cells have many diverse roles. Experimental observations support this hypothesis, implicating a role for mast cells not only in allergic diseases, but also many other diverse physiological, pathological, and immunological processes including tissue remodelling, wound repair, pathological fibrosis, arthritis, angiogenesis, and host reactions to neoplasia [2]. What has not been so clear until recently was how the mast cell might contribute to many of these processes based on its known profile of mediators (Table 1). The identification of human mast cells as a source of a plethora of cytokines and enzymes has revitalised interest in the role of this cell in immunology and pathology.

Section snippets

Mast cell cytokines

The explosion in cytokine biology in recent years has seen an escalating number of cytokines identified in an increasing range of cells, so it was perhaps inevitable that mast cells too would prove to be the source of these ubiquitous messenger proteins. The first hint that mast cells could produce cytokines was provided by the demonstration that many Abelson murine leukaemia virus (A-MuLV)-transformed mouse mast cell lines constitutively expressed granulocyte-macrophage colony-stimulating

Human mast cell cytokines in immunopathology

Because of the difficulty in obtaining human mast cells for study, and the paucity of mast cell-deficient humans, detailed knowledge of the role that mast cells play in human health and disease is relatively underdeveloped. Animal models of human disease are probably misleading and unhelpful in many instances, particularly as human and rodent mast cells differ in so many ways both phenotypically and pharmacologically. In vitro studies using human cells and mediators can provide clues, but may

Mast cell interactions with the specific immune system

Mast cells are generally considered to form part of the non-specific or innate immune system which provides the first line of defence against tissue damage. This will be considered in more detail later. This review will first focus on recent evidence which links the mast cell with the development of specific immunity.

Mast cells in inflammation and repair

Tissue remodelling in normal healthy tissue is dependent upon continuous turnover of structural tissue elements. This requires dissolution of structural matrix proteins, and the laying down of new structural components. Acute tissue injury by immunological, mechanical, physical or chemical stimuli is followed by the acute inflammatory response which classically consists of early vascular changes producing active hyperaemia and oedema, followed later by emigration of leukocytes, which are

Summary

The mast cell is a virtual pharmacopoeia of biological substances. It used to be believed that mast cell activation was all-or-nothing, with IgE cross-linking inducing symptoms of allergy and anaphylaxis. However, the activity of mast cells in health and disease is clearly much more complicated than this. The discovery that human mast cells secrete many pleiotropic cytokines suggested there may be many novel mast cell functions, and many of these are now being realised. The ubiquitous

Peter Bradding graduated from the University of Southampton, UK, in 1985. He studied cytokine expression in asthma for his postdoctoral thesis with Professor Stephen Holgate in Southampton, identifying mast cells as the predominant source of immunoreactive ‘Th2'-cytokines in the human bronchial mucosa. He is currently a Wellcome Trust Advanced Fellow and Honorary Senior Lecturer at the University of Leicester, and a specialist in general internal and respiratory medicine at Glenfield Hospital,

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    • Cited by (0)

    Peter Bradding graduated from the University of Southampton, UK, in 1985. He studied cytokine expression in asthma for his postdoctoral thesis with Professor Stephen Holgate in Southampton, identifying mast cells as the predominant source of immunoreactive ‘Th2'-cytokines in the human bronchial mucosa. He is currently a Wellcome Trust Advanced Fellow and Honorary Senior Lecturer at the University of Leicester, and a specialist in general internal and respiratory medicine at Glenfield Hospital, Leicester. Current research interests include mast cell-epithelial interactions in the pathogenesis of asthma, and ion channel regulation of mast cell hypersecretion in asthma.

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