INTRODUCTION Airborne particles with aerodynamic diamaters of less than 2 ym penetrate the bronchioles and alveolar regions of the lung (30). These particles may arise from viable sources such as bacteria and viral spores and anthropogenic sources such as cigarette smoke@ chemical mists@ fumes and dusts (42). It is thought that the sterility of the lower respiratory tract is maintained by pulmonary alveolar macrophage (PAM) (21). Evidence suggests that several steps are involved in PAM clearance of foreign material. First@ irritation to the lower respiratory tract stimulates an influx of macrophages to the alveolar regions of the lung (1). This process appears to be significant@ since in cases where influx does not occur clearance is impaired (6). Second@ when macroghages come into contact with inhaled particles they will try to phagocytose them. Their success is dependent on the physiocheraical properties of the particle and the activation state of the PAM. Third@ macrophages are able to inactivate ingested bacteria and break down other foreign material which has been phagocytosed (16). Finally@ it is thought that macrophages clear particles by moving toward the cilliated terminal bronchi@ or entering the lymphatic system (42). All the mechanisms of macrophage clearance are not completely understood@ but it is thought that chemotaxis'may play a role in macrophage movement during clearance activity. Chemotaxis is the movement of cells toward the source of a chemical gradient in their environment (54). Guinea pig alveolar macrophages respond chemotactically to synthetic-N-formyl peptides which are similar to metabolic products of bacteria (17). It seems possible@ therefore@ that PAM may be stimulated to move toward inhaled bacteria in a directed manner. Also it has been shown that human PAM respond to gradients of a protein extracted from lung lavage fluid (15). Chemical gradients in the lung could direct movement of particle laden macrophage to various sites in the lung where the cells may be removed@ i.e.@ the cilliated epithelium of the terminal bronchi or the lymphatic system. Exposure to cigarette smoke and air pollution are associated with an increased susceptibility to bacterial infection (4@ 16@ 19). Since PAM are the primary defense mechanism of the lower air ways@ it Is thought that cigarette smoke and air pollution may impair PAM clearance. In order to assess the validity of this hypothesis a variety of protocols have been developed to assess the effects of tobacco smoke and pollutants on PAM clearance function. Intact animals have been exposedin vivo to test aerosols for varying amounts of time. After exposure@ assessment of PAM function has been done using eitherin vivo or in vitro assays. Resistance to infection@ bacteriocidal activity and number of cells in lung lavage are in vivo assessments which can be made. Assays of PAM chemotaxis@ phagocytosis@ H2O2 and O2 release during phagocytosis@ glucose metabolism@ ATP consumption and cytotoxicity are some of the in vitro assessments made@ PAH may also be exposed to test material in vitro and tested using the in vitro assays listed above. Rats and mice are the preferred animals for experiments using in vivo exposure techniques for several reasons. First@ there is a large amount of information available relating to their susceptibility to infectious disease and air pollutants (4@ 27). In addition@ large numbers of animals can be used in one experiment allowing for statistical analysis of experimental results. House and rat PAM are usually not used for in vitro exposure experiments since many animals are required to get a sufficient number of cells. Also mouse PAM cannot be maintained in culture as successfully as PAM from other species (4). Rabbit PAM are the preferred cell type for in vitro exposure regimes. Large numbers of PAM can be harvested from one animal and these cells can easily be maintained in culture (4). Human PAM can be used to study in vivo effects of cigarette smoke or accidental exposure to toxic atmospheres on PAM function. Here PAM are harvested from the exposed Individuals and in vitro assessments of PAM function are made. These experiments are limited by difficult access to materials@ inability to control experimental conditions@ and low number of experimental subjects. Human PAM can also be used for in vitro exposure studies. These studies are also limited by difficult access to materials and low number of experimental subjects. Results from recent studies using these techniques are summarized below.
API PUBL 31-30265-1983 history
1983API PUBL 31-30265-1983 STIMULATION AND INHIBITION OF CHEMOTAXIS IN ABELSON VIRUS TRANSFORMED MACROPHAGES