This image taken with an electron microscope shows both the electron dense granule cores (examples shown by arrows) and the lucent granule matrix (examples shown by arrows) surrounding the cores in an eosinophil isolated from the blood of a healthy human. The bilobed nucleus is also evident. Original magnification X7000.
Photomicrograph of an eosinophil incubated with media only for 4 hours. Minimal degranulation seen, most granules still intact (see arrows for examples).
Photomicrograph of an eosinophil incubated with 100 micrograms/ml of an Alternaria extract for 4 hours. Notice extensive degranulation of nearly all of the granules (see arrows for examples).
Figure is modified from copyright © 2003 Mosby Inc. For more details, see Miike S and Kita H, Human eosinophils are activated by cysteine proteases and release inflammatory mediators. Journal of Allergy and Clinical Immunology, Vol. 111:704-13, 2003.
With in vitro models, we have been identifying and investigating the stimuli involved in eosinophil activation and how eosinophil functions are regulated by cell surface receptors, their ligands, and intracellular signaling pathways. Eosinophils from healthy people can be stimulated and examined in the laboratory for chemical changes inside the cell and even for changes within small intracellular structures called granules.
When eosinophils become activated, biochemically toxic substances within these granules are released.
This activation and release process likely involves regions of the cell becoming less acidic while the granules simultaneously become more acidic. The immunoglobulin called secretory IgA, which is very common in mucosal tissues (for example the respiratory and digestive systems), exerted distinctive responses on eosinophils. With one form of secretory IgA, eosinophils became fully activated and would be able to damage tissues, but another form of secretory IgA would prolong the lives of eosinophils and does not activate their destructive capacities. In other studies, eosinophil activation was dependent on one or more protease receptors.
Several animal models are also used to evaluate the physiologic significance of the in vitro observations. In a study where the mice had been treated for 5 days to induce a digestive system model of human colitis (inflammation of the colon), an abundance of eosinophils in the colons of genetically altered mice was associated with less damage and evidence of disease compared to the extensively damaged colons in normal mice with fewer eosinophils in their colon tissues. Thus, the presence of eosinophils is not enough to damage tissues, but other factors and signals are involved in complicated biological processes. Some processes lead to damage and other processes lead to normality. We continue to investigate the mediators and signaling molecules that are involved in these processes.