The influence of quartz and surfactant on immune responses

Sammanfattning: Pulmonary surfactant is a mixture of lipids and proteins that embeds the alveolar cells, has surface tension reducing properties but also influences the immune response. To further investigate this, quartz was used to initiate an inflammatory response in two different models. Firstly, in vitro exposures of resting and activated human leukocytes to combinations of quartz and surfactant were done, and secondly in vivo exposures of rats to instilled quartz were performed. We investigated expression of complement receptors (CR), made functional analyses of metabolic activity, phagocytosis and adhesion, and evaluated morphology. Resting blood granulocytes incubated with a porcine surfactant preparation had an increased expression of CR3 whereas monocytes were unaffected. Surfactant exposure of leukocytes decreased PMA-induced metabolic activation, possibly as a scavenger effect. Exposure of fMLP-activated human granulocytes to quartz reduced CR1 expression. Surfactant abolished this reduction, but if stored at elevated temperatures there was no corresponding protection. The effect is at least partly due to the content of Iysophosphatidylcholine, which increases over time. Summarising, intact surfactant seems to be required for preserving the CR1 expression. After a single intratracheal quartz instillation rat lungs were examined at five weeks and three months. Alveolar (AM) and interstitial macrophages (IM) were separated to study alterations during early inflammation and subsequent fibrosis, and to describe any compartmental differences. Alveolar recruitment of neutrophils was early prominent, and after three months also Iymphocytes accumulated. Three months after exposure AM adhered less to surfaces coated with extracellular matrix components, while the adherence was unaffected after five weeks. The receptor-independent metabolic activity (PMA) was lower for exposed AM than controls in both studies. This may indicate a downregulation of the inflammatory response in the lungs, possibly reflecting adoptive mechanisms to prevent the reaction from being self-destructive. AM expression of the functional receptors for MHC class ll (OX-6) and CR3 (OX-42) was increased post-exposure. The enhanced expression possibly results from newly recruited cells. Interstitial changes were consistent with an early fibrosing process. The adhesion was uninfluenced five weeks after exposure, but after three months exposed IM adhered more to the extracellular matrix component vitronectin. This could be related to remodelling. Five weeks after quartz instillation the IM receptor expression of MHC class ll (OX-6) was increased. However, it was unaffected after three months, maybe because an early peak in receptor expression had already passed at that stage. CR3 (OX-42) was only increased after three months, underlining the importance of transmigration and cell recruitment to the interstitium during the fibrosing process. The studies undertaken on AM and IM after induction of an inflammatory reaction present some differences in morphology, phenotype and function between the two compartments. Addition of surfactant did not alter the outcome. The two studies are of descriptive character but, as they were performed at different periods of time after the insult, the findings also reflect the dynamic evolution. Concluding, there are in vitro indices of surfactant's influence on inflammatory responses which in vivo studies may be masked for various reasons, e.g. turnover of surfactant. Key words: alveolar macrophages, complement receptor 1 and 3, interstitial macrophages, Iysophosphatidylcholine, phospholipids, quartz, rats, receptor expression, surfactant.