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Immune response to zymosan-induced pulmonary inflammation in rats.

Young-S; Roberts-JR; Antonini-JM
Toxicologist 2005 Mar; 84(Suppl 1):192
1->3-B-Glucans have been associated with increased pulmonary inflammation in mold-related indoor air problems. The objective of the present investigation was to determine the immune response to zymosan-induced pulmonary inflammation in SD rats. Rats received a single dose of zymosan A (2.5 mg/kg body weight) via intratracheal instillation (IT) and were euthanized on days 1, 4, 6, and 8 post IT. Inflammation and lung injury were assessed by measuring (1) neutrophil (PMN) infiltration into bronchoalveolar lavage fluid (BALF) and (2) albumin, total protein and lactate dehydrogenase levels in BALF. Alveolar macrophage activation was determined by chemiluminescence (CL). Immune response was investigated via immunophenotyping of lymphocytes and lymphokine production. Immunophenotyping was performed on BAL cells and lung-associated lymph node cells. Lymphokine production was measured from lymph node cells with or without concanavalin A stimulation by an enzyme-linked immunosorbent assay. Upon challenge with zymosan, rats exhibited increased inflammation and injury at the early time points post-IT exposure. Although elevations in PMN infiltration and CL had returned to control levels on day 4, lung-associated lymphocytes continued to proliferate and reached a maximum on day 6. The ratio of CD4 to CD8 T cells in the lymph node and BAL was lower in zymosan-treated rats than in control rats, indicating a greater increase in CD8 T cells as compare to CD4 T cells. Zymosan also increased the number of infiltrating NK cells, B cells, and T cells in BAL at all time points. B cells in BALF were found to be highest in number on day 1 for zymosan-treated rats. The ratio of T/B cells in BALF increased significantly on day 6 and 8. Zymosan treatment increased IL-2, IL-10 and IFN„ but not IL-4 production in lymphocytes. These data along with immunophenotyping of lymphocytes suggests that helper CD4 T and cytotoxic CD8 T cells are involved in the immune activation caused by zymosan treatment. In summary, rats exposed to zymosan had increased inflammation and altered lymphocyte profile, indicating an activation of innate and/or adaptive immune response in rats.
Immune-reaction; Laboratory-animals; Animals; Animal-studies; Pulmonary-system-disorders; Molds; Air-contamination; Air-quality; Lymph-nodes; Exposure-levels; Exposure-assessment; Lung; Respiratory-system-disorders; Indoor-air-pollution; Microorganisms; Indoor-environmental-quality
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The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana