Immunomodulation of local and systemic immunity after subchronic pulmonary exposure of mice to benzo(a)pyrene.

A single intratracheal (i.t.) instillation of 3H-BaP (2.5 mg/kg) cleared rapidly from the lung with a half life of approximately 8 h. In contrast, the amount of 3H-BaP (expressed as counts/min/mg tissue) in the lung-associated lymph nodes (LALN) continued to increase over a 6 day period while a low, persistent level of BaP was detected in the spleen. To determine whether humoral immunity was affected by BaP accumulation in lymphoid organs, B6C3F1 mice were given seven daily i.t. instillations of 0.4, 4.0 or 40 mg BaP/kg, and immunized with sheep red blood cells (SRBC) 1 day after the last BaP instillation. When antigen was given by i.t. instillation, the number of antigen-specific, antibody-forming cells (AFC) decreased in the LALN after BaP exposure. Interestingly, the number of AFC in the LALN from BaP-exposed mice were significantly increased after intraperitoneal (i.p.) immunization. However, these same mice had lower numbers of AFC in the spleen. When 51Cr-SRBC were instilled in the lung, the pulmonary clearance of radiolabeled antigen was slowed in BaP-exposed mice. When 51Cr-SRBC were placed in the peritoneal cavity, the amount of radiolabeled antigen that reached the LALN was similar in BaP-exposed and vehicle mice. However, four times more radiolabeled antigen translocated from the peritoneal cavity to the lung in BaP-exposed mice, while significantly less antigen reached the spleen and liver. Thus, BaP-induced immunomodulation of the humoral immune response appears to be influenced by the route of immunization, as well as by the proximity of the responding lymphoid tissue to the site of BaP deposition.