Eosinophil Adhesion to Cholinergic IMR-32 Cells Protects against Induced Neuronal Apoptosis

Abstract

Eosinophils release a number of mediators that are potentially toxic to nerve cells. However, in a number of inflammatory conditions, such as asthma and inflammatory bowel disease, it has been shown that eosinophils localize to nerves, and this is associated with enhanced nerve activity. In in vitro studies, we have shown that eosinophil adhesion via neuronal ICAM-1 leads to activation of neuronal NF-κB via an ERK1/2-dependent pathway. In this study, we tested the hypothesis that eosinophil adhesion to nerves promotes neural survival by protection from inflammation-associated apoptosis. Exposure of differentiated IMR-32 cholinergic nerve cells to IL-1β, TNF-α, and IFN-γ, or culture in serum-deprived medium, induced neuronal apoptosis, as detected by annexin V staining, caspase-3 activation, and DNA laddering. Addition of human eosinophils to IMR-32 nerve cells completely prevented all these features of apoptosis. The mechanism of protection by eosinophils was by an adhesion-dependent activation of ERK1/2, which led to the induced expression of the antiapoptotic gene bfl-1. Adhesion to nerve cells did not influence the expression of the related genes bax and bad. Thus, prevention of apoptosis by eosinophils may be a mechanism by which these cells regulate neural plasticity in the peripheral nervous system.

Neuroimmune crosstalk in asthma: Dual role of the neurotrophin receptor p75NTR

“…Thus it is suggested that immune cell-derived mediators cause depolarization of neurons and decrease their membrane resistance, 29 potentiate transmitter release, 30 and promote survival. 31 Conversely, activated afferent nerve fibers amplify airway inflammation by means of local release of neuropeptides, which then is also termed neurogenic inflammation. 7 Neuropeptides promote the chemotaxis, activation, and degranulation of eosinophils; increase lymphocyte proliferation and adhesion; and cause an imbalance in T H 1/T H 2-derived cytokines in favor of a T H 2 profile.…”

ADRB3 Adrenergic Receptor Is a Key Regulator of Human Myometrial Apoptosis and Inflammation During Chorioamnionitis1

“…The multidomain proapoptotic proteins BAX and BAK together constitute a requisite gateway to apoptotic cell death, because cells doubly deficient for these proteins are resistant to several different intrinsic death stimuli [15]. Therefore, BAX, BCL2, and cleaved CASP3 are widely used to assess apoptosis [16,17].…”

Diverse Effects of Eosinophil Cationic Granule Proteins on IMR-32 Nerve Cell Signaling and Survival

“…Recently, we have shown that eosinophil adhesion to IMR-32 cells confers protection on nerve cells from apoptosis induced either by proinflammatory cytokines (tumor necrosis factor, IL-1␤, and interferon-␥) or by serum deprivation (17). This is consequent to eosinophil adhesion to IMR-32 cells because eosinophil membrane preparations, which lacked eosinophil granule products, conferred similar protection to that provided by whole eosinophils.…”

“…This is consequent to eosinophil adhesion to IMR-32 cells because eosinophil membrane preparations, which lacked eosinophil granule products, conferred similar protection to that provided by whole eosinophils. Protection was dependent on adhesion via both ICAM-1 and VCAM-1 and on ERK 1/2 but not p38 activation (17). Having identified the role of surface adhesion per se, we have now attempted to identify the actions of the products released from the eosinophils.…”