Modulation of human alveolar macrophage properties by ozone exposure in vitro

We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O 3) (0.1 – 1.0 ppm for 2–4 hr). The functions studied reflect concern that O 3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O 3 caused a concentration-dependent increase in release of prostaglandin E 2 (PGE 2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O 3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O 2 −) production in response to phorbol ester was reduced after exposure of HAM to O 3 while the basal O 2 − release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O 3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-α, interleukin 1, and interleukin 6 were not induced by exposure to O 3. However, compared to controls, O 3-exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O 3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O 3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE 2 suggest that the effect of O 3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O 3-exposed individual.