Eosinophils are granulocytic leukocytes that originate in bone marrow. They are so called because their granules, which contain arginine-rich basic proteins, are colored bright orange by the acidic stain eosin. In healthy humans, these cells represent less than 6% of the leukocytes in the circulation; most eosinophils are found in tissues, especially in the connective tissue immediately underneath respiratory, gut, and urogenital epithelium, implying a likely role for these cells in defense against invading organisms at these sites. They possess numerous cell-surface receptors, including receptors for cytokines (such as IL-5), Fcγ and Fcα receptors, and the complement receptors CR1 and CR3, through which they can be activated and stimulated to degranulate. For example, parasites coated with IgG, C3b, or IgA can cause eosinophil degranulation. In allergic tissue reactions, the large concentrations of IL-5, IL-3, and GM-CSF that are typically present are likely to contribute to degranulation.
When activated, eosinophils express two kinds of effector function. First, they can release highly toxic granule proteins and free radicals, which can kill microorganisms and parasites but also can cause significant damage to host tissues in allergic reactions (Fig. 14.10). Second, they can synthesize chemical mediators, including prostaglandins, leukotrienes, and cytokines. These amplify the inflammatory response by activating epithelial cells and by recruiting and activating more eosinophils and leukocytes. In chronic inflammatory responses, eosinophils can contribute to airway tissue remodeling.
What were later to be defined as eosinophils were observed in the 19th century in the first pathological description of fatal status asthmaticus (an episode of severe asthma that does not respond to treatment and leads to respiratory failure and death), but the precise role of these cells in allergic disease generally is still unclear. In allergic tissue reactions, for example, those that lead to chronic asthma, mast-cell degranulation, and TH2 activation cause eosinophils to accumulate in large numbers and to become activated. Among other things, eosinophils secrete TH2-type cytokines and in vitro can promote the apoptosis of TH1 cells by their expression of IDO and consequent production of kynurenine, which acts on the TH1 cells. Their apparent promotion of TH2cell expansion may thus be partly due to a relative reduction in TH1-cell numbers. The continued presence of eosinophils is characteristic of chronic allergic inflammation, and eosinophils are thought to be major contributors to tissue damage. However, the observation that eosinophils accumulate at sites where there are high levels of cell turnover and considerable local stem-cell activity bolsters a growing consensus that eosinophils play an important role in restoring tissue homeostasis after infection and other types of tissue damage.
The activation and degranulation of eosinophils is strictly regulated, because their inappropriate activation is harmful to the host. The first level of control acts on the production of eosinophils by the bone marrow. Few eosinophils are produced in the absence of infection or other immune stimulation. But when TH2 cells are activated, cytokines they produce such as IL-5 and GM-CSF increase the production of eosinophils in the bone marrow and their release into the circulation. However, transgenic animals overexpressing IL-5 have increased numbers of eosinophils (eosinophilia) in the circulation but not in their tissues, indicating that the migration of eosinophils from the circulation into tissues is regulated separately, by a second set of controls. The key molecules in this case are the CC chemokines that have been named eotaxins because of their specificity for eosinophils: CCL11 (eotaxin 1), CCL24 (eotaxin 2), and CCL26 (eotaxin 3).