Nitric Oxide in Both Bronchoalveolar Lavage Fluid and Serum Is Associated With Pathogenesis and Severity of Antigen-Induced Pulmonary Inflammation in Rats

Abstract

Background. Nitric oxide (NO) is considered as a hallmark for allergic airway inflammation in asthmatics and animal models. But the correlation between NO and antigen-induced pulmonary inflammation (AIPI), a rat model for asthma, in varying genetic background population has not been completely understood. Objective. The objective in this study is to observe the different responsiveness to AIPI in two commonly used inbred rat strains and verify the correlation between NO from different sources and pathological parameters of AIPI by using Dark Agouti (DA), E3, F1 (E3 × DA), and F2 rat populations. Methods. AIPI was induced by systemically immunizing and intranasally challenging E3, DA, F1 (DA × E3), and F2 rats with ovalbumin (OVA). Pathological changes and mucus secretion in lungs were observed after hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining, whereas eosinophils in bronchoalveolar lavage fluid (BALF) were counted after Giemsa staining. Delayed-type hyperresponsiveness was determined by subcutaneous injection of OVA in ear. Total immunoglobulin E (IgE) and OVA-specific IgG1 were detected with enzyme-linked immunosorbent assay (ELISA). NO concentration was measured by the Griess method. Results. DA rats were unresponsive to OVA treatment, whereas E3 rats were susceptible to AIPI. F1 rats manifested the same responsiveness to OVA treatment as DA rats, and individual F2 rats showed the variable severity of AIPI. NO concentration in BALF and serum was significantly elevated in E3 rats but not in DA and F1 rats after OVA treatment. In F2 rats, NO concentration in serum was positively correlated with eosinophils in BALF, total IgE, and pathological scores, whereas NO concentration in BALF correlated only with eosinophils in BALF and total IgE. Conclusion. DA and F1 rats are resistant, whereas E3 rats are sensitive, to AIPI. NO in serum can represent the severity of allergic inflammation and pathological changes in lungs in F2 population.

Keywords :

• antigen-induced pulmonary inflammation
• DA rats
• eosinophils
• F2 population
• nitric oxide

Acknowledgments

The work was supported by grants from the National Natural Science Foundation of China (30801027, 30630058, and 30571725) and Shaanxi Province International Cooperation Foundation of China (2007-KW-06).