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Antibiotic uptake by alveolar macrophages of smokers
Abstract:
Cigarette smoking, particularly when associated with chronic pulmonary disease, increases the risk of respiratory tract infection. Thus, we elevated the uptake of antibiotics by alveolar macrophages (AM) obtained by bronchoalveolar lavage from persons who smoke and have associated pulmonary abnormalities, circumstances which adversely affect certain macrophage functions. The entry of radiolabeled drugs into AM was determined by a velocity-gradient centrifugation technique, and uptake was expressed as the ratio of cellular to extracellular antibiotic concentration (C/E). Cefamandole and penicillin G were taken up poorly by the AM obtained from smokers (C/E less than or equal to 1). Cellular levels of isoniazid, gentamicin, and tetracycline were similar to their extracellular concentrations. The lipid-soluble drugs lincomycin, chloramphenicol, and rifampin were concentrated severalfold by the AM from smokers (C/E = 3 to 11). Ethambutol also entered macrophages readily (C/E = 11). Erythromycin and clindamycin were massively concentrated by the AM from smokers (C/E = 23 to 56). The AM of smokers accumulated a lipid-soluble antibiotic (rifampin) and actively transported agents (erythromycin propionate, clindamycin) more avidly than did the AM of nonsmokers. Augmented uptake of these antibiotics by the AM of smokers may be related to structural and functional alterations induced by smoking.
Insights
Smoking impairs alveolar macrophage antibiotic uptake, especially for certain drugs. Smokers
Area of Science:
- Pharmacology
- Immunology
Background:
- Cigarette smoking, especially with chronic pulmonary disease, elevates respiratory tract infection risk.
- Certain macrophage functions are adversely affected by smoking-associated pulmonary abnormalities.
Purpose of the Study:
- To determine the effect of smoking on antibiotic uptake by alveolar macrophages (AM).
- To investigate how smoking-induced alterations in AM affect drug accumulation.
Main Methods:
- Alveolar macrophages (AM) were obtained from smokers and non-smokers via bronchoalveolar lavage.
- Uptake of radiolabeled antibiotics was measured using velocity-gradient centrifugation.
- Uptake was quantified as the cellular to extracellular antibiotic concentration ratio (C/E).
Main Results:
- Poor uptake (C/E ≤ 1) of cefamandole and penicillin G by smokers' AM.
- Similar cellular and extracellular concentrations (C/E ≈ 1) for isoniazid, gentamicin, and tetracycline.
- Concentrated uptake (C/E = 3–11) of lipid-soluble drugs (lincomycin, chloramphenicol, rifampin) and ethambutol.
- Massively concentrated uptake (C/E = 23–56) of erythromycin and clindamycin by smokers' AM.
- Smokers' AM showed greater accumulation of lipid-soluble and actively transported antibiotics compared to non-smokers'.
Conclusions:
- Smoking significantly alters alveolar macrophage antibiotic accumulation.
- Augmented uptake of specific antibiotics by smokers' AM may stem from smoking-induced structural and functional changes.