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Dose-dependent thiol and immune responses to ovalbumin challenge in Brown Norway rats

HELD, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

Joseph KH Ma

School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA

Daniel M Lewis

HELD, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

Jane YC Ma

HELD, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

Mark W Barger

HELD, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

Paul D Siegel

HELD, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA, pds3{at}cdc.gov

Dose-dependent specific antibody production, antigen-dependent pulmonary inflammation, and thiol changes in the lung and associated lymph nodes were examined in a Brown Norway rat model of pulmonary sensitization. Cysteine (CYSH), glutathione (GSH), and markers of inflammation in bronchoalveolar lavage fluid (BALF) were measured following ovalbumin (OVA) inhalation challenge. Alveolar macrophages (AM) and pulmonary-associated lymph node cells (LNC) were isolated and intracellular CYSH and GSH assessed. OVA-specific IgE and IgG antibodies were quantified from sera. A dose-dependent biphasic response was noted with respect to OVA-specific IgE. OVA-specific IgG concentrations were maximal at 68 mg (OVA)/m³. OVA challenge to sensitized rats induced increases in BALF albumin, total protein, lactate dehydrogenase, CYSH and GSH that were independent of serum antibody concentrations. AM thiols were modestly elevated at low OVA challenge doses, but sharply reduced at the higher OVA challenge doses. In contrast, both thiols were dose dependently elevated in BALF. CYSH, but not GSH, was elevated in LNC of OVA challenged rats. In summary, antigen exposure caused a dose-dependent alteration of inflammatory, thiol and immune parameters in OVA sensitized and challenged rats. Changes in thiol levels did not correlate with antibody responses. While the results of the present study do not support a functional role for thiols in the immune response, it is important to note the dose-dependent dramatic alteration seen in thiols following sensitization and challenge.

Key Words: alveolar macrophage • immunoglobulins • ovalbumin • parathymic and tracheal lymph nodes • thiols

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