Chitosan nanoparticle-mediated de novo synthesis of a novel natriuretic hormone peptide reverses established asthma in mice

• Published in: Journal of allergy and clinical immunology Vol. 113; no. 2; p. S325
• Main Authors: Singam, R.V., Kong, X., Hellerman, G., Juan, H.San, Behera, S., Zhang, W., Jena, P.K., Lockey, R.F., Mohapatra, S.S.
• Format: Journal Article
• Language: English
• Published: St. Louis Mosby, Inc 01.02.2004; Elsevier Limited
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.01.673

A family of natriuretic hormone peptides (NHP) with broad physiologic effects on the lung and cardiovascular system has been described. A novel peptide of pro-atrial natriuretic factor, NHP 73-102, causes long-lasting bronchoprotective effect in a prophylactic model of asthma and shows anti-inflammatory activity (Kumar et al, JACI, 2002; Hellerman et al, JACI, 2003). The potential of this peptide in ameliorating established asthma and its immunomodulatory effects was examined in this study using a murine model of allergen [ovalbumin (Ova)]-respiratory syncytial virus (RSV) infection-induced asthma. Mice were sensitized and challenged with Ova and then infected with RSV prior to their intranasal treatment with chitosan nanoparticles either expressing the plasmid encoded peptide (CHIpP) or incorporating NHP 73-102 (CHIP). Lung inflammation was examined by analyses of bronchoalveolar lavage and lung histology. Airway hyperreactivity (enhanced pause, Penh) was measured by whole body plethysmography. Cytokines were measured by intracellular cytokine staining (ICS). Therapy with CHIpP reversed Ova-induced airway reactivity (% Penh, P<0.01), pulmonary infiltration as evidenced by a decrease in the % of eosinophils (P<0.05), neutrophils and lymphocytes in the BAL of CHIpP-treated mice compared to controls, and pulmonary pathology as revealed by lung histology. ICS analysis of anti-CD3-stimulated splenocytes of these mice showed a significant decrease in the production of both IFN-g and IL-4 (P<0.01) by CD4+T cells. In contrast, CD4+ Tcells producing IL-10 significantly increased (P<0.05) in treated mice. Thus, de novo expression of NHP 73-102 reverses established asthma suggesting that this peptide may be useful as a novel therapy for asthma.