Repeated exposure to 1-->3-beta-glucan suppresses lung defense responses and slows the pulmonary clearance of listeria monocytogenes in rats.
Young-S; Roberts-JR; Antonini-JM
Toxicologist 2007 Mar; 96(1):104
Chronic exposure to low levels of mold has been reported to increase susceptibility to respiratory infections. Currently, the mechanism is not well understood. This study investigated lung defense effects after repeated low-dose zymosan (a 1-->3-beta-glucan from yeast cell wall) exposure on bacterial infection (Listeria monocytogenes) in male Sprague-Dawley rats. On days 0, 3, 7 and 10, rats received one dose of zymosan A (0.6 mg/kg body weight each dose) via intratracheal instillation or vehicle control (saline). On day 17 (one week later), rats were intratracheally inoculated with 5x105 bacteria. Rats were euthanized on days 20, 22, and 24. Bacterial clearance was determined by measuring colony-forming units cultured from the left lungs. Bronchoalveolar lavage (BAL) was performed on the right lungs. Inflammation and lung injury were assessed by measuring (1) neutrophil (PMN) infiltration and (2) albumin and lactate dehydrogenase levels in BAL fluid. Multiple zymosan treatments induced greater lung injury and inflammation as indicated by elevations in PMN, LDH, and albumin at days 22 and 24 compared to control. In addition, repeated low-dose exposure to zymosan slowed the clearance of the bacteria at day 20 and 22 compared to controls, suggesting a possible suppression in lung immune responses. In contrast, previous results have shown that a single acute dose of zymosan at a concentration (2.5 mg/kg body-weight) equivalent to the total of the four repeated concentrations used in the current study enhanced lung immune responses and increased the rate of bacterial clearance from the lung. This study demonstrated the importance of treatment concentration and dosing regimen in understanding lung immune effects associated with 1-->3-beta-glucan exposure.
Laboratory-animals; Animal-studies; Biodynamics; Pulmonary-disorders; Pulmonary-function-tests; Pulmonary-system-disorders; Alveolar-cells; Lung-cells; Lung-irritants; Lung-function; Chemical-analysis; Chemical-indicators; Chemical-reactions
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina