The effect of lung-derived neutrophils on alveolar macrophage function. Final report of a project funded by the British Lung Foundation

During inflammation, neutrophils are recruited to the alveolar region of the lung where they are in close proximity to the alveolar macrophages normally present there. Neutrophils have a powerful array of secretions which affect other cells and so we sought to examine whether neutrophil products had the ability to modulate key functions of alveolar macrophages implicated in the defence of the alveolar region.Neutrophil products were obtained by eliciting a neutrophil-rich exudate in rat lung by instillation of a heat killed preparation of Corynebacterium parvum; the population lavaged from the lung 16 hours after this insult was 70-90% neutrophils. These cells were cultured overnight in the absence or presence of the following potential triggers of neutrophil secrection:- PMA, zymosan, quartz and titanium dioxide; a lysate of the cells was also used. The supernatants collected following these treatments were then tested for their effects on the following activities of control alveolar macrophages:- phagocytosis, oxidant production, chemotaxis, spreading and proliferation.Neutrophil products did not influence oxidant production or phagocytosis except for a small enhancement of 125 I zymosan phagocytosis by macrophages treated with products from neutrophils exposed to quartz. The PMA in the PMA supernatant however caused inhibition of both oxidant production and phagocytosis. Neutrophil supernatant had a small but observable inhibitory effect on macrophage chemotaxis and spreading; once again contaminating PMA in the PMA triggered supernatant was particularly active in causing inhibition. Neutrophil supernatants had a variable but marked ability to enhance uptake of thymidine by alveolar macrophages; this uptake of DNA precursor was not however matched by an increase in cell number.The results suggest that neutrophils in inflamed alveoli are not likely to greatly affect the functions of alveolar macrophages by release of their products. The exceptions to this are a possible enhancement of alveolar macrophage phagocytic activity caused by quartz triggered neutrophils in quartz – inflamed lung and possible involvement of a neutrophil product as a source of signal for initiation of the DNA synthesis phase of the macrophage cell cycle. Other signals are clearly necessary, however, in order to induce the macrophage to divide completely.