Assessment of the molecular basis of the proallergenic effects of cigarette smoke

Epidemiological studies indicate a link between smoking and increased risk of immunoglobulin E-mediated allergies and asthma. The molecular basis underlying cigarette smoke related respiratory disorders are ill defined, but it is known that mast cells in the mucosal lining of the airways are an important reservoir of proinflammatory mediators, which play a pivotal role in the development of these diseases. The establishment of a novel cell exposure unit facilitated a study of mast cell responses to pollutants in mainstream cigarette smoke at the air/cell interface. Our study shows that cigarette smoke, but not filtered clean air, induces the release of mediators of type I hypersensitivity responses and stimulates the synthesis of proinflammatory cytokines, including interleukin (IL)-4, 5, 10, and 13 and tumor necrosis factor (TNF)-α, in cells of mast cell lineage. These results explain how exposure to pollutants present in cigarette smoke can induce the pathophysiological responses associated with allergy, IgE-mediated and IgE-independent asthma since IL-4 and IL-13 induce class switching to IgE, and IL-13 has recently been identified as the key mediator of IgE-independent asthma

Protein and cell engineering of components of the human receptor/effector system : applications for therapy and diagnosis

Adaptive immune responses characterised by the synthesis of antibodies of the immunoglobulin E (IgE) isotype play an important role in type I hypersensitivity disorders and parasitic infestations, diseases which have an significant socio-economic impact world-wide. This paper considers potential applications of recent advances in our understanding of the origin of isotype specific immune responses which emerged as a result of cell and protein engineering studies on components of the human IgE/receptor/effector system. Furthermore, the identification of the receptor binding regions in IgE as a result of the development of a stable assay system has important applications for the design of rational therapeutic interventions in allergy and asthma, the treatment of mast cell tumours, and the establishment of procedures for the selective isolation of cells expressing the high-affinity receptor for IgE for functional studies