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Inhibition of candidacidal activity of polymorphonuclear cells by alveolar macrophage-derived factor from lung cancer
A Vecchiarelli1, M Dottorini, T Beccari
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
Culture supernatants of alveolar macrophages (AM) from lung cancer patients are able to inhibit the candidacidal activity of polymorphonuclear cells (PMN) in vitro. This phenomenon is ascribed to a factor secreted in the culture medium by unstimulated AM from tumor-bearing patients, but not from normal subjects. The inhibitor does not apparently affect the phagocytic activity of PMN, but the superoxide release during phagocytosis is significantly impaired when cells are pretreated with supernatants containing the factor. The secretion of the inhibitor seems to be restricted to the pulmonary compartment of lung cancer patients, since culture supernatants of peripheral blood monocytes (PBM) from the same subjects are not capable of depressing the candidacidal activity of PMN. The AM-derived factor is not inactivated after exposure to heat (60 degrees C) and when supernatants are analyzed by HPLC, the inhibitory activity is recovered in the fractions corresponding to a low molecular weight (800 D). In conclusion, AM from lung cancer patients are able to produce a factor capable of inhibiting the antimicrobial activity of PMN. This could account, at least in part, for the enhanced susceptibility to local infections observed in lung cancer patients.
Insights
Alveolar macrophages (AM) from lung cancer patients secrete a factor that impairs polymorphonuclear cell (PMN) antimicrobial activity. This lung cancer-related immune dysfunction may increase infection susceptibility.
Area of Science:
- Immunology
- Oncology
- Infectious Diseases
Background:
- Lung cancer patients exhibit increased susceptibility to local infections.
- Alveolar macrophages (AM) play a role in pulmonary immune responses.
Purpose of the Study:
- To investigate the effect of AM from lung cancer patients on polymorphonuclear cell (PMN) antimicrobial function.
- To identify the nature of the inhibitory factor secreted by AM.
Main Methods:
- In vitro culture of AM from lung cancer patients and healthy subjects.
- Assay of candidacidal activity and superoxide release of PMN after incubation with AM culture supernatants.
- Heat stability and molecular weight determination (HPLC) of the inhibitory factor.
Main Results:
- AM from lung cancer patients secreted a factor inhibiting PMN candidacidal activity.
- This factor impaired superoxide release during phagocytosis but not phagocytic activity itself.
- The inhibitor was heat-stable, low molecular weight (~800 D), and AM-specific (not from peripheral blood monocytes).
Conclusions:
- AM in lung cancer patients produce a factor that suppresses PMN antimicrobial function.
- This AM-derived inhibitor may contribute to the increased risk of infections in lung cancer patients.