Purified Rat IgG1 Kappa Isotype Control Antibody (Low Endotoxin, Azide-Free) Functional Grade

The aim of this study was to determine if mice exposed to Aspergillus (A.)fumigatus spores develop airway inflammation in a similar manner to Recurrent Airway Obstruction (RAO) in horses. Different groups of 2-, 5-, 6- and 8-month-old Rockefeller (RK) mice were used throughout the experiment. The mice were maintained in the animal house for 16 days and kept in cages containing hay contaminated with A. fumigants. After 16 days of mold exposure, the mice were bled and sacrificed to obtain bronchoalveolar lavage fluid (BALF) or lung tissues for histological analysis. In addition, we measured the levels of A. fumigatus-specific antibodies by ELISA. The results demonstrated that inhalation of A. fumigants spores in mice induced an inflammatory response in the lungs that was characterized by peribronchiolar and perivascular mononuclear infiltration and bronchiolar luminal exudates. Moreover, there was extensive folding of the airway epithelia, which is a sign of airway smooth muscle contraction and smooth muscle hypertrophy. In addition, we observed a high number of neutrophils and an increase in IgE, IgG1 and IgG2a antibodies in the BALF from mice that were older than 5 months and were exposed to A. fumigatus. These animals recovered from their respiratory distress when they were placed in a remission environment. We conclude that simple exposure of mice to moldy hay induces a condition that is similar to RAO in horses. Therefore, using this mouse model for the study of equine RAO offers the opportunity to approximate the immunologic response to airborne irritants and allergens as well as to evaluate pharmacological therapies.

The present study was performed to elucidate the roles of serum anti-Sm antibodies in the pathogenesis of systemic lupus erythematosus (SLE). Highly purified peripheral blood monocytes obtained from healthy donors were cultured in the presence of monoclonal anti-Sm antibody (anti-Sm mAb), monoclonal anti-U1 -RNP antibody (anti-RNP mAb) or control murine IgG1 or IgG3. After various periods of incubation, levels of IL-6 and TNF-alpha in the culture supernatants were measured by ELISA and the expression of mRNA for various molecules in monocytes was determined using RT-PCR. Flow cytometry analysis confirmed the bindings of anti-Sm mAb and anti-RNP mAb on viable human monocytes. Both anti-Sm mAb and anti-RNP mAb significantly increased the production of IL-6 and TNF-alpha of human monocytes in a dose-dependent manner, although the latter was more potent than the former. Of note, anti-Sm mAb synergistically enhanced the production and mRNA expression of IL-6 and TNF-alpha of human monocytes in the presence of anti-RNP mAb. Notably, anti-RNP mAb, but not anti-Sm mAb, significantly enhanced the mRNA expression of ReIA in human monocytes. Finally, anti-Sm mAb still up-regulated the IL-6 production of monocytes in the presence of anti-RNP mAb under the influence of N-acetyl cysteine or pyrrolidine dithiocarbamate that totally abrogated the IL-6 production provoked by anti-Sm mAb alone in the absence of anti-RNP mAb. These results demonstrate that anti-Sm and anti-RNP antibodies synergistically up-regulate the expression of IL-6 and TNF-alpha in human monocytes. The data also suggest that the effect of anti-Sm in the synergy with anti-RNP might not involve NFkB activation.