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

Morgan, Ross; Costello, Richard W.; Durcan, Niamh; Kingham, Paul J.; Gleich, Gerald J.; McLean, W. Graham; Walsh, Marie Therese

doi:10.1165/rcmb.2005-0056oc

Cited by 38 publications

(29 citation statements)

References 38 publications

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“…Previous studies and our own preliminary studies indicated that co-culture of eosinophils with IMR32 cells did not lead to significant apoptosis of either the nerves or the eosinophils when they were maintained in coculture for as long as 96 h (12). Indeed, we have shown that eosinophils and their degranulation proteins protect IMR32 cells from apoptosis (52,53). Second, to avoid potential contamination by gene products contained within eosinophils, mRNA extracted from eosinophils was subjected to RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil-Mediated Cholinergic Nerve Remodeling

Durcan

Costello²,

McLean³

et al. 2006

Am J Respir Cell Mol Biol

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Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling. We hypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M 2 muscarinic receptor, with this induction being mediated via an adhesion-dependent release of eosinophil proteins, including major basic protein and nerve growth factor. Studies on the promoter sequence of the M 2 receptor indicated that this induction was initiated at a transcription start site 145 kb upstream of the gene-coding region. This promoter site contains binding sites for a variety of transcription factors including SP1, AP1, and AP2. Eosinophils also induced the expression of several cholinergic genes involved in the synthesis, storage, and metabolism of acetylcholine, including the enzymes choline acetyltransferase, vesicular acetylcholine transferase, and acetylcholinesterase. The observed eosinophil-induced changes in enzyme content were associated with a reduction in intracellular neural acetylcholine but an increase in choline content, suggesting increased acetylcholine turnover and a reduction in acetylcholinesterase activity, in turn suggesting reduced catabolism of acetylcholine. Together these data suggest that eosinophil localization to cholinergic nerves induces neural remodeling, promoting a cholinergic phenotype.

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Section: Discussionmentioning

confidence: 99%

Eosinophil-Mediated Cholinergic Nerve Remodeling

Durcan

Costello²,

McLean³

et al. 2006

Am J Respir Cell Mol Biol

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“…Although a possible involvement of endogenous autacoids cannot be completely ruled out in the present study because certain potent mediators (e.g., PGE 2 or PGI 2 ) may still be released from isolated neurons or from nonneuronal satellite cells present in the culture (25,39,49), other potential contributing factors should also be considered. For example, it is possible that the sustaining action of MBP is related to cascades of intracellular signaling events triggered by the cationic protein in these neurons (37). In addition, a recent study has further revealed that the binding of MBP with certain specific cell-surface receptors plays an important role in its cytostimulatory and cytotoxic properties (18), which may explain, perhaps in part, why the sensitizing effect on the pulmonary neurons in the present study persisted even after MBP was completely washed out of the recording chamber.…”

Section: Discussionmentioning

confidence: 99%

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Gu¹,

Wiggers²,

Gleich³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gu Q, Wiggers ME, Gleich GJ, Lee L-Y. Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins. Am J Physiol Lung Cell Mol Physiol 294: L544-L552, 2008. First published January 4, 2008 doi:10.1152/ajplung.00271.2007.-It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318 -1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 M, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked ϳ10 min after MBP and lasted for Ͼ60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-L-glutamic or poly-L-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e.g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions. major basic protein; eosinophil cationic protein; eosinophil peroxidase; airway inflammation; airway hypersensitivity ASTHMA IS CHARACTERIZED BY chronic airway inflammation associated with airway infiltration of various inflammatory cells, particularly the eosinophils (7). Activated eosinophils are known to secrete a number of cationic proteins, including major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) (16). Previous studies have shown that intratracheal instillation of eosinophil-derived cationic proteins such as MBP induces bronchoconstriction and bronchial hyperresponsiveness in a number of animal species (9,17,21). Similar effects can also be induced by intratracheal administration of synthetic cationic proteins such as poly-Llysine (PLL) (10,24,46).Most of the sensory inputs arising from airways and lungs are conducted in vagus nerves and their branches. Cell bodies of these sensory nerves reside in two adjacent but distinct anatomic structures, the nodose and intracranial jugular ganglia. It is known that Ͼ75% of vagal bronchopulmonar...

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“…The increase in the level of eosinophils in the blood of exposed mice can be associated with inflammation in the respiratory systems, allergy and asthma (Morgan et al 2005). According to Kurosky et al (2009), eosinophils are granulocytic leucocytes that function in diverse inflammatory and immunoregulatory processes.…”

Section: Discussionmentioning

confidence: 99%

Effects of gas flaring on blood parameters and respiratory system of laboratory mice, Mus musculus

Otitoloju

Dan-Patrick

2010

Environmentalist

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In order to evaluate the potential harmful effects of gas flaring on mammals, albino mice, Mus musculus, were exposed to gas flares for 8 weeks under laboratory conditions. The effect of gas flaring on blood parameters includes a reduction in white blood cell counts among mice exposed to 8-h daily of gas flaring when compared to control mice. The red blood cells also showed varied abnormalities such as stacked erythrocytes (rouleaux formation), crenated (spicule) cells and teardrop cells (dacrocytes). The detection of the increasing level of eosinophils in the blood of mice exposed to gas flares was observed to be indicative of a degenerative disease condition and usefulness as a good marker of pollution for monitoring, and early detection of adverse effects of gas flares was recommended. Histopathological examination of the lungs of exposed mice revealed distortions in the segmental bronchus and alveoli of the respiratory organ, with interspersed brown pigments and polymorphonuclear cells, which were absent in the controls. The environmental implications including the health hazards posed by the exposure of mammals to gas flares in crude oil production areas were discussed.

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

Cited by 38 publications

References 38 publications

Eosinophil-Mediated Cholinergic Nerve Remodeling

Eosinophil-Mediated Cholinergic Nerve Remodeling

Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins

Effects of gas flaring on blood parameters and respiratory system of laboratory mice, Mus musculus

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