Interstrain variation in murine susceptibility to inhaled acid-coated particles

Epidemiologic studies have demonstrated a positive correlation between conc entration of acid aerosol and increased morbidity and mortality in many urb an environments. To determine whether genetic background is an important ri sk factor for susceptibility to the toxic effects of inhaled particles, we studied the interstrain (genetic) and intrastrain (environmental) variance of lung responses to acid-coated particle (ACP) aerosol in nine strains of inbred mice. A flow-past nose-only inhalation system was used to expose mic e to ACPs produced by the cogeneration of a carbon black aerosol-sulfur dio xide (SO2) mixture at high humidity. Three days after a single 4-h exposure to ACPs or filtered air, mice underwent bronchoalveolar lavage, and cell d ifferentials and total protein were determined as indexes of inflammation a nd epithelial permeability, respectively. To determine the effect of ACPs o n alveolar macrophage (AM) function, lavaged AMs were isolated from exposed animals and Fe receptor-mediated phagocytosis was evaluated. Compared with air-exposed animals, there was a slight but significant exposure effect of ACPs on the mean number of lavageable polymorphonuclear leukocytes in C3H/ HeJ and C3H/HeOuJ mice. ACP exposure also caused a significant decrease in AM phagocytosis. Relative to respective air-exposed animals, Fc receptor-me diated phagocytosis was suppressed in eight of nine strains. The order of s train-specific effect of ACPs on phagocytosis was C57BL/6J > 129/J > SJL/J > BALB/cJ > C3H/HeOuJ > A/J > SWR/J > AKR/J. There was no effect of ACP exp osure on AM phagocytosis in C3H/HeJ mice. The significant interstrain varia tion in AM response to particle challenge indicates that genetic background has an important role in susceptibility. The effects of ACPs on AM functio n, inflammation, and epithelial hyperpermeability were not correlated (i.e. , no cosegregation). This model may have important implications concerning interindividual variation in particle-induced compromise of host defense.