Skip to main content Accessibility help

Comparison of arginase isoform expression in patients with different subtypes of chronic rhinosinusitis

  • T Taruya (a1), S Takeno (a1), K Kubota (a1), A Sasaki (a1), T Ishino (a1) and K Hirakawa (a1)...



Although human paranasal sinuses are critical organs for nitric oxide production, little information is available regarding the role of arginase in alterations of arginine metabolism and nasal nitric oxide levels that may be informative for classifying chronic rhinosinusitis subtypes.


The expression and localisation of arginase and nitric oxide synthase isoforms in paranasal sinus mucosa were examined, and the fractional exhaled nitric oxide was measured in chronic rhinosinusitis without nasal polyps (n=18) and chronic rhinosinusitis with nasal polyps (n = 27) patients.


Increased arginase-2 activities in chronic rhinosinusitis without nasal polyps patients were associated with significantly lower levels of nasal fractional exhaled nitric oxide. Chronic rhinosinusitis with nasal polyps patients showed significant NOS2 messenger RNA upregulation with concomitant higher levels of oral and nasal fractional exhaled nitric oxide.


These results indicate that fractional exhaled nitric oxide is a valid marker for differentiating chronic rhinosinusitis phenotypes based on a delicate balance between arginase and nitric oxide synthase activities in nitric oxide production.


Corresponding author

Address for correspondence: Dr S Takeno, Department of Otolaryngology, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan Fax: +81 82 257 5254 E-mail:


Hide All
1Lundberg, JO, Weitzberg, E. Nasal nitric oxide in man. Thorax 1999; 54:947–52
2Maniscalco, M, Sofia, M, Pelaia, G. Nitric oxide in upper airways inflammatory diseases. Inflamm Res 2007;56:5869
3Dweik, RA, Boggs, PB, Erzurum, SC, Irvin, CG, Leigh, MW, Lundberg, JO et al. An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602–15
4Maarsingh, H, Zaagsma, J, Meurs, H. Arginine homeostasis in allergic asthma. Eur J Pharmacol 2008;585:375–84
5Luiking, YC, Ten Have, GA, Wolfe, RR, Deutz, NE. Arginine de novo and nitric oxide production in disease states. Am J Physiol Endocrinol Metab 2012;303:E117789
6Maarsingh, H, Zaagsma, J, Meurs, H. Arginase: a key enzyme in the pathophysiology of allergic asthma opening novel therapeutic perspectives. Br J Pharmacol 2009;158:652–64
7Maarsingh, H, Dekkers, BG, Zuidhof, AB, Bos, IS, Menzen, MH, Klein, T et al. Increased arginase activity contributes to airway remodelling in chronic allergic asthma. Eur Respir J 2011;38:318–28
8Zimmermann, N, King, NE, Laporte, J, Yang, M, Mishra, A, Pope, SM et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003;111:1863–74
9Lara, A, Khatri, SB, Wang, Z, Comhair, SA, Xu, W, Dweik, RA et al. Alterations of the arginine metabolome in asthma. Am J Respir Crit Care Med 2008;178:673–81
10Lindberg, S, Cervin, A, Runer, T. Nitric oxide production in the upper airways is decreased in chronic sinusitis. Acta Otolaryngol 1997;117:113–17
11Ragab, SM, Lund, VJ, Saleh, HA, Scadding, G. Nasal nitric oxide in objective evaluation of chronic rhinosinusitis therapy. Allergy 2006;61:717–24
12Fokkens, WJ, Lund, VJ, Mullol, J, Bachert, C, Alobid, I, Baroody, F et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012; 50:112
13Nakayama, T, Yoshikawa, M, Asaka, D, Okushi, T, Matsuwaki, Y, Otori, N, et al. Mucosal eosinophilia and recurrence of nasal polyps – new classification of chronic rhinosinusitis. Rhinology 2011;49:392–6
14Yoshimura, K, Kawata, R, Haruna, S, Moriyama, H, Hirakawa, K, Fujieda, S et al. Clinical epidemiological study of 553 patients with chronic rhinosinusitis in Japan. Allergol Int 2011;60:491–6
15Takeno, S, Taruya, T, Ueda, T, Noda, N, Hirakawa, K. Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis. Auris Nasus Larynx 2013;40:458–64
16Lund, VJ, Mackay, IS. Staging in rhinosinusitus. Rhinology 1993;31:183–4
17American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171:912–30
18Noda, N, Takeno, S, Fukuiri, T, Hirakawa, K. Monitoring of oral and nasal exhaled nitric oxide in eosinophilic chronic rhinosinusitis: A prospective study. Am J Rhinol Allergy 2012;26:255–9
19Arnal, JF, Flores, P, Rami, J, Murris-Espin, M, Bremont, F, Pasto, I et al. Nasal nitric oxide concentration in paranasal sinus inflammatory diseases. Eur Respir J 1999;13:307–12
20Moncada, S, Palmer, RM, Higgs, EA. Biosynthesis of nitric oxide from L–arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 1989;38:1709–15
21Cho, WS, Kim, TH, Kim, KH, Lee, HM, Lee, SH, Ju, YH et al. Increased expression of arginase I and II in allergic nasal mucosa. Laryngoscope 2011;121:236–40
22Ceylan, E, Aksoy, N, Gencer, M, Vural, H, Keles, H, Selek, S. Evaluation of oxidative–antioxidative status and the l–arginine–nitric oxide pathway in asthmatic patients. Respir Med 2005;99:871–6
23Unal, M, Eskandari, HG, Erçetin, N, Doğruer, ZN, Pata, YS. Serum nitrite/nitrate and arginase levels in patients with allergic rhinitis. ORL J Otorhinolaryngol Relat Spec 2007;69:113–15
24Yamamoto, M, Tochino, Y, Chibana, K, Trudeau, JB, Holguin, F, Wenzel, SE. Nitric oxide and related enzymes in asthma: relation to severity, enzyme function and inflammation. Clin Exp Allergy 2012;42:760–8
25Ratjen, F, Döring, G. Cystic fibrosis. Lancet 2003;361:681–9
26Grasemann, H, Schwiertz, R, Matthiesen, S, Racke, K, Ratjen, F. Increased arginase activity in cystic fibrosis airways. Am J Respir Crit Care Med 2005;172: 1523–8
27Yamashiro, Y, Shimizu, T, Oguchi, S, Shioya, T, Nagata, S, Ohtsuka, Y. The estimated incidence of cystic fibrosis in Japan. J Pediatr Gastroenterol Nutr 1997;24:544–7


Related content

Powered by UNSILO

Comparison of arginase isoform expression in patients with different subtypes of chronic rhinosinusitis

  • T Taruya (a1), S Takeno (a1), K Kubota (a1), A Sasaki (a1), T Ishino (a1) and K Hirakawa (a1)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.