EFFECT OF BLOOD LEUKOCYTE DEPLETION ON THE INFLAMMATORY RESPONSE OF THE LUNG TO QUARTZ

This study determined the effect of blood leucocyte depletion on the early inflammatory response of the lung to α-quartz. F344 N rats were instilled intratracheally with either physiological saline or 2 or 5 mg of α-quartz suspended in saline. One day prior to the instillation, half of the rats received an ip injection of rabbit antiserum that had been raised against rat neutrophils. The other half of the rats received an ip injection of normal rabbit serum. One day after the instillation of saline or quartz, the animals were euthanized and observed for changes in blood cell numbers, lung histopathology, and bronchoalveolar lavage fluid (BALF) content of indicators of an inflammatory response and cytotoxicity. The rabbit antiserum depleted the blood of most white blood cells of all types. BALF fluid from saline-instilled animals did not differ between the white blood cell-depleted and the nondepleted animals except for a 20% reduction in numbers of alveolar macrophages in the depleted animals. BALF fluid from the nondepleted, quartz-instilled animals had a dose-dependent increase in content of neutrophils and protein (indicator of an increase in the permeability of the alveolar/capillary barrier) as well as an increase in lactate dehydrogenase and glutathione reductase (cytoplasmic enzymes whose presence extracellularly indicates cytotoxicity), alkaline phosphatase (indicator of type II cell secretory activity), β-glucuronidase, and acid proteinase (lysosomal enzymes) activities. The higher dose of quartz also elicited an increase in LTB4 and PGE2 content of BALF. GSH content of BALF was decreased by the quartz exposure. The depletion of blood white blood cells prevented the influx of neutrophils into the alveoli of the quartz-exposed rats and decreased the BALF markers of capillary permeability and cytotoxicity (protein content and extracellular cytoplasmic enzymes). The absence of neutrophils in the alveoli had no effect on the lysosomal content of BALF, indicating that the neutrophils were not the source of these enzymes in nondepleted rats exposed to α-quartz. The quartz-induced elevation of LTB4 in BALF was not observed in depleted rats, suggesting that neutrophils may be the source of the increase in this leukotriene in the BALF. Both the GSH content and the alkaline phosphatase activity in BALF were enhanced in the absence of alveolar neutrophils. The enhancement of GSH in BALF is consistent with the neutrophils being the source of reactive oxygen species that deplete GSH. The increased alkaline phosphatase activity in the BALF of both the depleted and nondepleted animals is consistent with the type II cell hypertrophy that was induced by quartz instillation and was neutrophil independent. The study provides information on the probable sources of some of the inflammatory mediators in BALF and suggests that neutrophils contribute to the acute toxicity accompanying the inflammatory response of the lung to quartz. The neutrophil is not required. however, for the production of type II cell hypertrophy. © 1991.