Abstract
We investigated the effect of asthmatic serum on constitutive eosinophil apoptosis in normal subjects. Eosinophil apoptosis in normal subjects was inhibited by asthmatic serum but not normal serum. In a detailed analysis based on the presence of house dust mite (HDM) IgE, HDM IgE-positive (+) asthmatic serum was more effective for eosinophil apoptosis than that of HDM IgE-negative (−) asthmatic serum. HDM IgE+ asthmatic serum inhibited both HDM IgE− and HDM IgE+ normal eosinophil apoptosis, and HDM IgE− asthmatic serum suppressed eosinophil apoptosis of HDM IgE+ normal. HDM IgE− normal serum did not inhibit either HDM IgE− or HDM IgE+ normal eosinophil apoptosis, and HDM IgE+ normal serum inhibited HDM IgE+ normal eosinophil apoptosis. The kind of HDM IgE (Dermatophagoides pteronissinus-specific IgE and Dermatophagoides farinae-specific IgE) was not related to the effect of asthmatic serum on eosinophil apoptosis. Extracts of DP and DF, Der p1, and Der p2, were not effective for eosinophil apoptosis. HDM IgE+ asthmatic serum inhibited cleavage of procaspase 9 and procaspase 3. Asthmatic serum induced Akt and ERK phosphorylation, and ERK activation was suppressed by AKTi. Taken together, asthmatic serum inhibited normal eosinophil apoptosis via PI3K/Akt/ERK cascade. The novel approach taken in this study provided better insight into HDM-associated anti-apoptotic mechanism of eosinophils in patients with asthma.
Similar content being viewed by others
References
Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, Wardlaw AJ, Pavord ID (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62:1043–1049
McGrath KW, Icitovic N, Boushey HA, Lazarus SC, Sutherland ER, Chinchilli VM, Fahy JV, Asthma Clinical Research Network of the National Heart, Lung, and Blood Institute (2012) A large subgroup of mild-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 185:612–619
Holgate ST (2008) Pathogenesis of asthma. Clin Exp Allergy 38:872–897
Gaffin JM, Phipatanakul W (2009) The role of indoor allergens in the development of asthma. Curr Opin Allergy Clin Immunol 9:128–135
Kawabata A, Kawao N (2005) Physiology and pathophysiology of proteinase-activated receptors (PARs): PARs in the respiratory system: cellular signaling and physiological/pathological roles. J Pharmacol Sci 97:20–24
Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8:205–217
Willart MA, Lambrecht BN (2009) The danger within: endogenous danger signals, atopy and asthma. Clin Exp Allergy 39:12–19
Fick RB Jr (1999) Anti-IgE as novel therapy for the treatment of asthma. Curr Opin Pulm Med 5:76–80
Simon HU (2009) Cell death in allergic diseases. Apoptosis 14:439–446
Ogawa Y, Duru EA, Ameredes BT (2008) Role of IL-10 in the resolution of airway inflammation. Curr Mol Med 8:437–445
Ueki S, Mahemuti G, Oyamada H, Kato H, Kihara J, Tanabe M, Ito W, Chiba T, Takeda M, Kayaba H, Chihara J (2008) Retinoic acids are potent inhibitors of spontaneous human eosinophil apoptosis. J Immunol 181:7689–7698
Bianchi SM, Dockrell DH, Renshaw SA, Sabroe I, Whyte MK (2006) Granulocyte apoptosis in the pathogenesis and resolution of lung disease. Clin Sci (Lond) 110:293–304
Lampinen M, Carlson M, Håkansson LD, Venge P (2004) Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy 59:793–805
Akuthota P, Xenakis JJ, Weller PF (2011) Eosinophils: Offenders or general bystanders in allergic airway disease and pulmonary immunity? J Innate Immun 3:113–119
Wegmann M (2011) Targeting eosinophil biology in asthma therapy. Am J Respir Cell Mol Biol 45:667–674
Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG (2011) Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS ONE 6:e25683
Kankaanranta H, Moilanen E, Zhang X (2005) Pharmacological regulation of human eosinophil apoptosis. Curr Drug Targets Inflamm Allergy 4:433–445
Yang EJ, Choi E, Ko J, Kim DH, Lee JS, Kim IS (2012) Differential effect of CCL2 on constitutive neutrophil apoptosis between normal and asthmatic subjects. J Cell Physiol 227:2567–2577
Stepensky P, Keller B, Buchta M, Kienzler AK, Elpeleg O, Somech R, Cohen S, Shachar I, Miosge LA, Schlesier M, Fuchs I, Enders A, Eibel H, Grimbacher B, Warnatz K (2013) Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J Allergy Clin Immunol 131:477–485
Szalai C, Ungvári I, Pelyhe L, Tölgyesi G, Falus A (2008) Asthma from a pharmacogenomic point of view. Br J Pharmacol 153:1602–1614
Gent JF, Belanger K, Triche EW, Bracken MB, Beckett WS, Leaderer BP (2009) Association of pediatric asthma severity with exposure to common household dust allergens. Environ Res 109:768–774
Lin YC, Su HJ, Hsiue TR, Lee CH, Chen CW, Guo YL (2002) Levels of house dust mite-specific IgE and cockroach-specific IgE and their association with lower pulmonary function in Taiwanese children. Chest 121:347–353
Albano PM, Ramos JD (2011) Association of house dust mite-specific IgE with asthma control, medications and household pets. Asia Pac Allergy 3:145–151
Saffar AS, Alphonse MP, Shan L, Hayglass KT, Simons FE, Gounni AS (2007) IgE modulates neutrophil survival in asthma: role of mitochondrial pathway. J Immunol 178:2535–2541
Acknowledgments
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2011-0013716).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, I.S., Kim, M.J., Kim, D.H. et al. Different anti-apoptotic effects of normal and asthmatic serum on normal eosinophil apoptosis depending on house dust mite-specific IgE. Mol Biol Rep 40, 5875–5881 (2013). https://doi.org/10.1007/s11033-013-2695-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-013-2695-z