Neurotrophin effects on eosinophils in allergic inflammation

Nassenstein, Christina; Braun, Armin; Nockher, Wolfgang Andreas; Renz, Harald

doi:10.1007/s11882-005-0039-3

Cited by 20 publications

(19 citation statements)

References 88 publications

(81 reference statements)

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“…The increased recruitment of eosinophils is a phenomenon of helminth and allergic diseases (4,16,17,22,27,33,36). Despite this, relatively few studies can assign a clear in vivo function to eosinophils.…”

Section: Discussionmentioning

confidence: 99%

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Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

Specht¹,

Saeftel²,

Arndt

et al. 2006

Infect Immun

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Eosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing of helminth parasites by their toxic granule products exists only in vitro. We investigated the in vivo roles of the eosinophil granule proteins eosinophil peroxidase (EPO) and major basic protein 1 (MBP) during infection with the rodent filaria Litomosoides sigmodontis. Mice deficient for either EPO or MBP on the 129/SvJ background developed significantly higher worm burdens than wild-type mice. Furthermore, the data indicate that EPO or MBP is involved in modulating the immune response leading to altered cytokine production during infection. Thus, in the absence of MBP, mice showed increased interleukin-10 (IL-10) production after stimulation of macrophages from the thoracic cavity where the worms reside. In addition to elevated IL-10 levels, EPO ؊/؊ mice displayed strongly increased amounts of the Th2 cytokine IL-5 by CD4 T cells as well as a significantly higher eosinophilia. Interestingly, a reduced ability to produce IL-4 in the knockout strains could even be seen in noninfected mice, arguing for different innate propensities to react with a Th2 response in the absence of either EPO or MBP. In conclusion, both of the eosinophil granule products MBP and EPO are part of the defense mechanism against filarial parasites. These data suggest a hitherto unknown interaction between eosinophil granule proteins, defense against filarial nematodes, and cytokine responses of macrophages and CD4 T cells.

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Section: Discussionmentioning

confidence: 99%

“…Eosinophils are a hallmark of allergic diseases (4,16,17,33,36) and helminth infection (22,27). It is has been debated whether they are involved directly in the killing of worms or in orchestrating the immune response (13,19,31,45).…”

mentioning

confidence: 99%

Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

Specht¹,

Saeftel²,

Arndt

et al. 2006

Infect Immun

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“…Although classically known for their effects on neurons, NTs are multifunctional growth factors and exert numerous effects including differentiation of B-lymphocytes (18), histamine release from mast cells (19), formation of intramyocardial blood vessels (20) and growth of follicles in the ovaries (21) on non-neuronal cells, particularly in immunocompetent cells and lymphoid organs (22). Interest in the NTs system has grown particularly in regards to several lung diseases (23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic value of neurotrophin expression in malignant pleural effusions

Duysinx

Paulus

Heinen

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in nonsquamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

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“…There are multiple sources of NGF in the lung, including bronchial epithelium, pulmonary fibroblasts, bronchial smooth muscle, and several inflammatory cells, including eosinophils (45). NGF expression is increased in eosinophils isolated from allergic patients (39,40), and NGF concentration is positively correlated with allergic disease severity, airway hyperreactivity, and eosinophil mediator release (38). NGF is known to mediate airway hyperreactivity by increasing substance P expression in sensory nerves (8,47).…”

mentioning

confidence: 99%

Atropine-enhanced, antigen challenge-induced airway hyperreactivity in guinea pigs is mediated by eosinophils and nerve growth factor

Verbout

Jacoby

Gleich

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Although anticholinergic therapy inhibits bronchoconstriction in asthmatic patients and antigen-challenged animals, administration of atropine 1 h before antigen challenge significantly potentiates airway hyperreactivity and eosinophil activation measured 24 h later. This potentiation in airway hyperreactivity is related to increased eosinophil activation and is mediated at the level of the airway nerves. Since eosinophils produce nerve growth factor (NGF), which is known to play a role in antigen-induced airway hyperreactivity, we tested whether NGF mediates atropine-enhanced, antigen challenge-induced hyperreactivity. Antibody to NGF (Ab NGF) was administered to sensitized guinea pigs with and without atropine pretreatment (1 mg/kg iv) 1 h before challenge. At 24 h after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Electrical stimulation of both vagus nerves caused bronchoconstriction that was increased in challenged animals. Atropine pretreatment potentiated antigen challenge-induced hyperreactivity. Ab NGF did not affect eosinophils or inflammatory cells in any group, nor did it prevent hyperreactivity in challenged animals that were not pretreated with atropine. However, Ab NGF did prevent atropine-enhanced, antigen challenge-induced hyperreactivity and eosinophil activation (assessed by immunohistochemistry). This effect was specific to NGF, since animals given control IgG remained hyperreactive. These data suggest that anticholinergic therapy amplifies eosinophil interactions with airway nerves via NGF. Therefore, therapeutic strategies that target both eosinophil activation and NGF-mediated inflammatory processes in allergic asthma are likely to be beneficial.

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Neurotrophin effects on eosinophils in allergic inflammation

Cited by 20 publications

References 88 publications

Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

Lack of Eosinophil Peroxidase or Major Basic Protein Impairs Defense against Murine Filarial Infection

Diagnostic value of neurotrophin expression in malignant pleural effusions

Atropine-enhanced, antigen challenge-induced airway hyperreactivity in guinea pigs is mediated by eosinophils and nerve growth factor

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