Modification of Macrophage Adhesion by Ozone : Role of Cytokines and Cell Adhesion Molecules^a

Abstract

The inflammatory response in the lungs following an inhalation exposure of animals and humans to ozone (O3) is associated with macrophage stimulation, release of chemotactic agents, and neutrophilia. This study investigated the adhesive behavior of the alveolar macrophages and its relevance to the inflammatory processes in the lung. Macrophages recovered by BAL from rats exposed to purified air or 0.8 ppm O3 were studied in vitro for their adhesion to epithelial cells derived from ARL-14. The macrophages from O3-exposed animals displayed greater adhesion to the epithelial cells than the macrophages from control rats exposed to purified air. The O3-induced adhesion was attenuated in the macrophages treated with a combination of interleukin-1 alpha and tumor necrosis factor-alpha antibodies (anti-IL-1+anti-TNF). The cell adhesion stimulated by O3 exposure was also attenuated when the macrophages were incubated in the presence of antibodies to leukocyte adhesion molecules, CD11b, or epithelial cell adhesion molecules, ICAM-1. A marginal increase in the surface expression of CD11b was noticed in macrophages from the rats exposed to O3. A similar change in the ICAM-1 expression was, however, not observed. The results suggest that the O3-induced modifications of macrophages are mediated by IL-1 and TNF, and that these modifications are accompanied by a minimal change in the expression of the cell-adhesion molecules.

The Failure of STAT6-deficient Mice to Develop Airway Eosinophilia and Airway Hyperresponsiveness Is Overcome by Interleukin-5

“…Macrophage numbers were significantly reduced in both STAT6-sufficient and -deficient mice. The reason for this is not clear but may reflect increased expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of activated macrophages leading to increased adhesion to the airway epithelium (19). These observations further support the role of the eosinophil in the development of AHR in this model and more importantly, establish the critical role of STAT6 in these responses.…”

The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

“…The selection of target proteins was based on previously published studies and tended to provide incremental advances in our understanding of the involved mechanisms. A case in point is the analysis of cytokines and chemokines that may be involved in ozone-induced inflammation [8,[40][41][42][43][44]. Studies of this type have only examined a handful of the dozens of cytokines that may potentially play a role in this process.…”

“…This type of unbiased approach is not dependent upon previously published studies and may be instrumental in generating specific novel hypotheses involving proteins and pathways that may not have been previously implicated in the process being studied. In the case of ozone-induced lung injury each of the studies described above has typically had a very narrow focus, and integrating all of these results into a unified understanding of the pathophysiology of ozone exposure has been difficult [8,[40][41][42][43][44].…”

Repetitive Pneumoperitoneum with Ozonized Oxygen as a Preventive in Lethal Polymicrobial Sepsis in Rats

“…Inhaled ozonized oxygen exhibits strong immune modulatory effects on the innate immune system especially on alveolar macrophages, but also on extrapulmonary macrophages [21][22][23][24]. Furthermore, ozonized blood in vitro causes a release of different cytokines such as TNF-·, GM-CSF, IL-2 or IFN-Á [25], but hitherto, no further data exist from in vivo experiments to find out if this gas mixture of ozonized oxygen has any detrimental or beneficial influence on the cytokine release by leucocytes.…”