Date of Award
6-1989
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biological Sciences
First Advisor
Peter Abramoff
Second Advisor
Walter Fredricks
Third Advisor
James Courtright
Fourth Advisor
Ann LeFever
Fifth Advisor
Peter Tonellato
Abstract
Evaluation of the immunological regulation of the normal acute inflammatory response can aid in understanding how importer regulation can lead to chronic disease. Cellular changes within the pulmonary interstitium and bronchoalveolar spaces of the lung were determined in an immune complex-mediated acute pulmonary inflammatory response in guinea pigs. PMN infiltration into the alveoli was observed by three hours after initiation of inflammation. The contribution of the chemoattractant, leukotriene B4 (LTB4), to this accumulation was studied. Increased levels of LTB4 were not observed in bronchoalveolar lavage fluids recovered from inflamed lungs at time points corresponding to increased PMN recovery. A role for LTB4 in PMN accumulation was postulated based on the observation of increased in vitro synthesis of LTB4 by alveolar cells recovered from inflamed lungs. Furthermore, in vivo inhibition of lipoxygenase activity prior to initiation of inflammation slightly suppressed subsequent PMN recovery. Accumulation of macrophages within the pulmonary interstitium and the alveoli of the inflamed lung was also assessed. Accumulation of macrophages was more extensive and persistent in the alveoli than within the interstitium and was first apparent at 12 hours after the initiation of inflammation. The chemokinetic motility of alveolar macrophages recovered at this stage of inflammation, measured in a linear under-agarose assay, was elevated relative to that of normal alveolar macrophages and those recovered later in the inflammatory response. These results suggest that increased motility of macrophages plays a role in their accumulation at sites of inflammation. Macrophages which have accumulated and become activated within the inflammatory environment are hypothesized to play an important role in initiating resolution of acute pulmonary inflammation. Maturation of both interstitial and alveolar macrophages prior to resolution of pulmonary inflammation was assessed by histochemical staining techniques and measurements of phagocytic activity. The early stages of the inflammatory response were characterized by the presence of immature macrophages in both interstitial and alveolar compartments. Subsequent maturation of these immature macrophages occurred prior to resolution of inflammation and was most extensive within the alveolar compartment. These results suggest that alveolar macrophages may figure more importantly than interstitial macrophages in resolving the inflammatory response.