Ozone Differentially Modulates Airway Responsiveness in Atopic Versus Nonatopic Guinea Pigs

Abstract

While acute exposures to ozone (O(3)) can alter airway responsiveness, effects from long-term exposures at low concentrations are less clear. This study assessed whether such exposures could induce nonspecific hyperresponsiveness in nonatopic (nonsensitized) guinea pigs and/or could exacerbate the pre-existing hyperresponsive state in atopic (sensitized) animals, and whether gender was a factor modulating any effect of O(3). Responsiveness was measured during and following exposures to 0.1 and 0.3 ppm O(3) for 4 h/day, 4 days/wk for 24 wk in male and female nonsensitized animals, those sensitized to allergen (ovalbumin) prior to initiation of O(3) exposures, and those sensitized concurrently with exposures. Ozone did not produce hyperresponsiveness in nonsensitized animals, but did exacerbate hyperresponsiveness to both specific and nonspecific bronchoprovocation challenges in sensitized animals, an effect that persisted through at least 4 wk after exposures ended. Gender was not a factor modulating response to O(3). Induced effects on responsiveness were not associated with numbers of eosinophils in the lungs nor with any chronic pulmonary inflammatory response, but were correlated with antigen-specific antibodies in blood. This study supports a role for chronic O(3) exposure in the exacerbation of airways dysfunction in a certain segment of the general population, namely, those demonstrating atopy.

Sensitivity to Ozone, Diesel Exhaust Particles, and Standardized Ambient Particulate Matter in Rats with aListeria Monocytogenes-Induced Respiratory Infection

“…This is confirmed by others who show that the atopic responses after co-exposure to an allergen and ozone are increased (Depuydt et al, 2002;Wagner et al, 2002;Iijima et al, 2001). This is also due to an imbalance of the Th1 and Th2 cells (Osebold et al, 1988;Schlesinger et al, 2002Schlesinger et al, a, 2002bSumitomo et al, 1990;Tsai 316 P. A. STEERENBERG ET AL. et al, 1998;Vargas et al, 1994).…”

“…Similar adjuvant potency was shown for other constituents of air pollution such as ambient PM or, more specifically, DEP in experimental animals and in humans when ovalbumin or pollen was used as the respiratory allergen (Diaz-Sanchez et al, 1997, 2002a, 2002bFujimaki et al, 1994Fujimaki et al, , 1995Fujimaki et al, , 2001Heo et al, 2001;Maejima et al, 1997;Steerenberg et al, 1999;Takafuji et al, 1989;van Zijverden et al, 2000). Most of these studies suggest that PM shifts the balance between Th1 and Th2 in favor of Th2-mediated responses.…”

“…Ozone-ovalbumin coexposures result in an adjuvant activity of ozone in mice, rats, and guinea pigs compared to the effect of the allergen alone (Depuydt et al, 2002;Wagner et al, 2002;Iijima et al, 2001;Osebold et al, 1988;Schlesinger et al, 2002aSchlesinger et al, , 2002bSumitomo et al, 1990;Tsai et al, 1998;Vargas et al, 1994). Some papers (Neuhaus-Steinmetz et al, 2000) have reported that ozone shifted the immune responses to ovalbumin toward a Th2-like pattern in both IgE high responders (BALB/c mice) and low responders (C57Bl/6 mice).…”

“…Experimental studies of animals with respiratory allergy show that ozone increases hyperresponsiveness to both specific and nonspecific bronchoprovocative challenges in sensitized animals (Schlesinger et al, 2002b;Goldsmith et al, 2002). Furthermore, it increases the IgE response in serum and the interleukin (IL)-4 and IL-5 levels in bronchoalveolar lavage (BAL), and it suppresses the Th1 antibody response (IgG2a) (Neuhaus-Steinmetz et al, 2000).…”

A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter.

“…Basal and serum-opsonized, zymosan-stimulated production of superoxide anion (O 2 •-) by pulmonary macrophages (Mø) was assessed using a microtiter plate assay based upon the reduction of ferricytochrome c (20). Proliferation of splenic T and B lymphocytes was measured in response to stimulation with concanavalin (Con) A and lipopolysaccharide (LPS), respectively (22).…”