Lung inflammation from repeated exposure to LPS and glyphosate.

Agricultural workplaces consist of multiple airborne contaminants and inhalation exposures induce respiratory effects in workers. Endotoxin (LPS) and glyphosate are two common airborne contaminants in agricultural environments. We have previously shown that exposure to a combination of LPS and glyphosate synergistically modulates immune reactions as compared to individual exposures. The immunopathogenesis of acute and chronic exposure to complex agricultural exposures including LPS and glyphosate is not known; therefore, we further investigated the lung cellular inflammatory differences in mice exposed to either a combination, or individual, LPS, and glyphosate for 1 day, 5 days, and 10 days. Exposure to a combination of LPS and glyphosate resulted in greater cellular inflammatory effects in lungs as compared to individual exposures to LPS or glyphosate. Repeated exposures to the combination of LPS and glyphosate resulted in robust infiltration of inflammatory cells in the perivascular, peribronchiolar, and alveolar regions, and increases of alveolar septal thicknesses and perivascular spaces in the lungs with intense intercellular adhesion molecule (ICAM) - 1 staining in the perivascular region, but minimal staining in the pulmonary artery endothelium.

Effects of elevated CO2 levels on lung immune response to organic dust and lipopolysaccharide.

Workplaces with elevated organic dust levels such as animal feed barns also commonly have elevated levels of gasses, such as CO2. Workers exposed to such complex environments often experience respiratory effects that may be due to a combination of respirable factors. We examined the effects of CO2 on lung innate immune responses in mice co-exposed to the inflammatory agents lipopolysaccharide (LPS) and organic dust. We evaluated CO2 levels at the building recommended limit (1000 ppm) as well as the exposure limit (5000 ppm). Mice were nasally instilled with dust extracts or LPS and immediately put into chambers with a constant flow of room air (avg. 430 ppm CO2), 1000 ppm, or 5000 ppm CO2 enriched air. Results reveal that organic dust exposures tended to show decreased inflammatory responses with 1000 ppm CO2 and increased responses at 5000 ppm CO2. Conversely, LPS with addition of CO2 as low as 1000 ppm tended to inhibit several inflammatory markers. In most cases saline treated animals showed few changes with CO2 exposure, though some changes in mRNA levels were present. This shows that CO2 as low as 1000 ppm CO2 was capable of altering innate immune responses to both LPS and organic dust extracts, but each response was altered in a different fashion.

Adhesion Molecules in Lung Inflammation from Repeated Glyphosate Exposures.

Glyphosate is an active ingredient in herbicides. Exposure to glyphosate-based herbicides has been associated with respiratory dysfunctions in agricultural workers. The ability of inhaled glyphosate to induce lung inflammation is not well understood. Further, the role of adhesion molecules in glyphosate-induced lung inflammation has not been studied. We evaluated lung inflammatory responses from single and repeated glyphosate exposures. Male C57BL/6 mice were intranasally exposed to glyphosate (1 µg/40 µL) for 1 day or once daily for 5 days or 10 days. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected and analyzed. Repeated exposure to glyphosate for 5 days and 10 days resulted in an increase in neutrophils in BAL fluid and higher eosinophil peroxidase levels in lungs, with leukocyte infiltration further confirmed through lung histology. Repetitive exposure to glyphosate increased IL-33 and Th2 cytokines IL-5 and IL-13. A single glyphosate treatment revealed expression for ICAM-1, VCAM-1, and vWF adhesion molecules in the perivascular region of lung sections; with repeated treatment (5 and 10 days), adhesion molecule expression was found in the perivascular, peribronchiolar, and alveolar regions of the lungs. Repetitive exposure to glyphosate induced cellular inflammation in which adhesion molecules may be important to the lung inflammatory process.

Pulmonary inflammatory response from co-exposure to LPS and glyphosate.

Agricultural airborne work exposures are complex in nature and workplace exposures are a risk for respiratory outcomes in workers. Endotoxin and glyphosate are two common agents in agricultural exposures. While endotoxin (lipopolysaccaride, LPS) is a potent inflammatory agent it explains only a portion of the respiratory inflammatory response. The inflammatory potential when LPS is presented with another common agricultural respiratory agent, glyphosate, is not known. METHODS: Mice were assigned to four treatment groups: control, LPS alone, glyphosate alone, glyphosate and LPS combined. Treatments were for 1, 5 or 10 days. RESULTS: Five days of repeated exposure to the comintation of LPS and glyphosate resulted in higher neutrophil counts, myloperoxidase, TNF-α, IL-6, KC levels, and ICAM-1 and TLR-2 expression compared to the same length of treatment to LPS or glyphosate alone. After 10-days of exposure, inflammatory responses decreased, however leukocyte infiltration persisted along with increases in IL-4. CONCLUSIONS: Glyphosate exposure modified LPS induced lung inflammatory responses and TLR-2 may be important in the modulated inflammatory response.