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Adriamycin impairs phagocytic function and induces morphologic alterations in human neutrophils
Abstract:
Normal human polymorphonuclear leukocytes (PMNL) were preincubated in vitro with methotrexate, 5-fluorouracil, vincristine, cisplatin, Adriamycin (doxorubicin), and daunomycin for 15 hours before being tested in a phagocytic-bactericidal assay. Anthracycline-treated PMNL were defective in phagocytosis and killing of the bacteria, in contrast to the other chemotherapeutic agents which allowed the PMNL to remain functional. The defect of Adriamycin-treated PMNL resulted from decreased ingestion: 3 micrograms/ml Adriamycin inhibited by 50% of the uptake of Oil Red-O particles. In this assay, the proportion of noningesting PMNL increased from less than or equal to 20% with 0.62 micrograms/ml to greater than or equal to 90% with 10 micrograms/ml Adriamycin. Electron microscopy revealed that Adriamycin-inactivated PMNL had rounded up, were depleted in glycogen, and had undergone profound nuclear changes. RNA and protein synthesis in PMNL were also affected. Adriamycin, besides producing neutropenia, may decrease the phagocytic function of circulating PMNL.
Insights
Adriamycin and daunomycin impair polymorphonuclear leukocyte (PMNL) function, hindering bacterial phagocytosis and killing. Other chemotherapy drugs did not affect PMNL function, suggesting specific toxicity from anthracyclines.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMNL) are crucial for innate immunity.
- Chemotherapeutic agents can have diverse effects on immune cells.
- Understanding drug-induced immune suppression is vital for patient care.
Purpose of the Study:
- To investigate the in vitro effects of various chemotherapy drugs on normal human PMNL function.
- To determine if anthracyclines, specifically Adriamycin (doxorubicin) and daunomycin, impact PMNL phagocytic and bactericidal capabilities.
Main Methods:
- Human PMNL were preincubated with methotrexate, 5-fluorouracil, vincristine, cisplatin, Adriamycin, and daunomycin.
- Phagocytic-bactericidal assays were performed to assess PMNL function.
- Oil Red-O particle uptake measured phagocytosis.
- Electron microscopy examined cellular morphology and ultrastructure.
Main Results:
- PMNL treated with Adriamycin and daunomycin exhibited defective phagocytosis and bacterial killing.
- Other tested chemotherapeutic agents did not impair PMNL function.
- Adriamycin significantly reduced particle ingestion in a dose-dependent manner.
- Electron microscopy revealed Adriamycin-induced PMNL morphological changes, including nuclear alterations and glycogen depletion.
Conclusions:
- Anthracyclines (Adriamycin, daunomycin) selectively impair PMNL phagocytic and bactericidal functions.
- Adriamycin's mechanism involves decreased particle ingestion and significant cellular damage.
- These findings suggest Adriamycin may contribute to decreased immune function in patients, beyond neutropenia.