Source of Alkaline Phosphatase Activity in Epithelial Lining Fluid of Normal and Injured F344 Rat Lungs

Abstract

In pulmonary toxicity screening tests in which the epithelial lining fluid (ELF) is sampled by bronchoalveolar lavage (BAL), investigators have observed both increases and decreases in alkaline phosphatase (AP) activity in BAL fluid during an acute inflammatory response. Such alterations in AP activity are difficult to interpret because of uncertainties concerning the source of the AP. It could be coming from type II cells, or from influxing neutrophils or serum, along with transudation of proteins due to the increased permeability of the alveolar capillary barrier. To aid in determining the source of AP activity in ELF during an acute inflammatory response, AP in ELF from control F344 rats was compared to AP in ELF from endotoxin-treated or quartz-treated rats and to AP in serum, type II cells, neutrophils, and lungs of untreated rats. The isoelectric focusing pattern and the inhibition by amino acids, a chelating agent, and heat were used to characterize the AP from the different sources. The AP in ELF from control and from inflamed lungs had similar characteristics and closely resembled AP in type II cells, total lung, and neutrophils. It was concluded that type II cells, and not neutrophils, were the major source of AP in ELF for two reasons: (1) The amount of AP activity in neutrophils was approximately 40-fold less than in type II cells, and (2) earlier studies indicated an enhanced increase in AP activity in ELF in neutrophil-depleted versus nondepleted rats in response to α-quartz. Current evidence from this study and others suggests that AP in ELF is associated with secreted surfactant, indicating that alterations in ELF levels of AP may mean changes in the rate of surfactant secretion or turnover. Time course studies on the alterations in AP activity in ELF in relation to histopathological changes in alveolar epithelia and surfactant secretion are needed to further interpret the significance of AP activity in ELF.