In pulmonary aspergillosis the host primarily relies upon alveolar phagocytic cells to remove conidia efficiently before germination. Neutrophils play a major role in clearing conidia from the lung. The mechanisms that regulate the recruitment of neutrophils in the respiratory tract of patients is unclear. It is well known that several chemotactic agents can enhance one or more of these effector functions of neutrophils. Two of these chemotactic agents are interleukin-8 (IL-8) and N-forrnylmethionyl-leucylphenylalanine (fmlp). Evidence in humans suggests that alveolar macrophages can initiate and drive the migration of PMNs into the lungs by releasing the macrophage-derived lymphokine IL-8. The effect of the chemoattractants, interleukin-8 (IL-8) and N formlymethionyl-leucylphenylalanine (fmlp) on neutrophil phagocytosis of serum-opsonised Aspergillus fumigatus conidia was studied. Preexposure of neutrophil monolayers to IL-8 (10-100 ng/ml) or fmlp 10'6M) for 20 min increased phagocytosis from 15% to 35%. Furthermore, there was a significant increase in the numbers of conidia ingested by active neutrophils. The chemoattractants did not enhance phagocytosis of conidia when added contemporaneously to neutrophil monolayers. The ability of each chemoattractant to act as a primer for the other was investigated. It was found that fmlp could prime for IL-8 and fmlp enhancement of phagocytosis, but IL-8 could not. An increase from 15% to 55% in phagocytosis was seen at a pre-exposure concentration of 10-5M fmlp followed by an incubation period of 30 min in the presence of 20 ng/ml IL-8. There was no significant increase in the average number of internalised conidia under these conditions. The response of human neutrophils to priming stimuli may have important implications in the pathogenesis of aspergillosis.
Full conference title:
The 2nd Meeting of the European Confederation of Medical Mycology
- ECMM 2nd (1995)