Adenosine: Key Link between Allergy and Asthma?

Mast cells are the main effector cell type of immunoglobulin E (IgE) -dependent immediate hypersensitivity responses manifested as seasonal rhinitis, urticaria and life threatening anaphylaxis-inducing food allergies [1]. The causative agents are pre-formed inflammatory mediators stored within cytoplasmic granules that are released immediately (degranulation) following activation, and lipid mediators such as prostaglandins and leukotrienes that are rapidly biosynthesized and secreted. Prolonged activation also results in delayed secretion of de novo produced cytokines that contribute to chronic disease by further activating and recruiting other cell types to the site of inflammation. In recent years, mast cells have been implicated in numerous other diseases in various mouse models. Whether mast cells are critical for disease development in all of these pathophysiological states, or if their involvement is artifactual to particular experimental animal models remains to be determined. In humans, however, considerable evidence exists to implicate mast cells in asthma pathogenesis [2,3]. Mast cells are known to infiltrate asthmatic smooth muscle, and are found in greater numbers in lungs of patients with asthma compared to non-asthmatics [3]. Moreover, it is now widely accepted that allergy is a major component of asthma. A recent clinical study showing that treatment with Omalizumab, an antibody against IgE, prevented nearly all increases in seasonal asthma and decreased allergy symptoms demonstrates the interwoven relationship between allergies and asthma [4]. This and other studies underscore the clinical significance of understanding the mechanisms that regulate mast cells and their role in allergy and asthma. Adenosine, a purine nucleoside and product of ATP metabolism, is a modulator of mast cell degranulation that has been implicated in asthma. The discovery over 30 years ago that adenosine could enhance the degranulation of rodent mast cells [5], and subsequent finding that inhalation or intravenous administration of adenosine induces mast cell-dependent bronchoconstriction in asthmatics [6-8] ignited a strong interest in adenosine as a possible link to asthma pathogenesis. Over the years, numerous studies have attempted to understand the mechanism (s) by which adenosine potentiates mediator release from mast cells and its involvement in pulmonary diseases. Yet, many issues remain unresolved and many questions unanswered. One major question is: Why does administered adenosine induce bronchoconstriction only in asthmatics with no pulmonary effects observed in non-asthmatic individuals? If adenosine acting on mast cells to enhance degranulation was solely responsible for inducing bronchospasm it would be expected that nonasthmatics would respond similarly to administered adenosine as asthmatics. However, this is not the case.