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Miconazole and amphotericin B alter polymorphonuclear leukocyte functions and membrane fluidity in similar fashions
K Yasui1, M Masuda, T Matsuoka
1Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Abstract:
The influence of miconazole on polymorphonuclear leukocytes (PMN) was investigated and compared with that of amphotericin B (AmB). Human PMN were preincubated in vitro with miconazole or AmB at therapeutically attainable concentrations in plasma, and their chemotactic functions were assessed with the synthetic chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). Changes in membrane fluidity of PMN were examined by an excimer-forming lipid technique. Adherence of PMN was measured by a nylon fiber column method. Miconazole and AmB pretreatment irreversibly depressed PMN random migration and chemotaxis under agarose but did not influence superoxide anion production. Both miconazole and AmB increased PMN adherence. Miconazole and AmB lowered the binding affinity of FMLP receptors on PMN and decreased the membrane fluidity in a similar manner. These results demonstrate that miconazole and AmB alter selected in vitro membrane properties of human PMN.
Insights
Miconazole and amphotericin B (AmB) impair polymorphonuclear leukocytes (PMN) function by altering their membrane properties. These antifungal drugs reduce PMN migration and adherence, impacting immune cell behavior.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells.
- Antifungal agents like miconazole and amphotericin B (AmB) can affect immune cell function.
- Understanding drug effects on PMNs is vital for managing infections.
Purpose of the Study:
- To investigate and compare the effects of miconazole and amphotericin B (AmB) on human polymorphonuclear leukocytes (PMNs).
- To assess how these antifungal drugs influence PMN chemotaxis, adherence, and membrane properties.
Main Methods:
- Human PMNs were preincubated with miconazole or AmB at therapeutic concentrations.
- Chemotaxis was assessed using N-formylmethionyl-leucyl-phenylalanine (FMLP).
- Membrane fluidity was measured using an excimer-forming lipid technique, and adherence was quantified via a nylon fiber column method.
Main Results:
- Miconazole and AmB pretreatment irreversibly reduced PMN random migration and chemotaxis.
- Both drugs increased PMN adherence.
- Miconazole and AmB decreased PMN membrane fluidity and lowered FMLP receptor binding affinity.
Conclusions:
- Miconazole and AmB significantly alter key in vitro membrane properties of human PMNs.
- These alterations in PMN function may have implications for host immune response during antifungal therapy.
- The study highlights the immunomodulatory effects of common antifungal medications.