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Effects of phagocytosis on antibiotic and nucleoside uptake by human polymorphonuclear leukocytes

T H Steinberg, W L Hand

    The Journal of Infectious Diseases
    |March 1, 1984
    PubMed

    Insights

    Phagocytosis significantly enhances clindamycin uptake by human polymorphonuclear leukocytes (PMNLs) via the nucleoside transport system. This study reveals a novel stimulation of membrane transport during phagocytosis.

    Area of Science:

    • Cell Biology
    • Pharmacology
    • Immunology

    Background:

    • Phagocytes, such as polymorphonuclear leukocytes (PMNLs), play a crucial role in combating infections, particularly those caused by facultative intracellular organisms.
    • Understanding how antibiotics interact with and enter phagocytic cells is vital for optimizing antimicrobial therapy.
    • Previous research has not fully elucidated the mechanisms governing antibiotic entry into phagocytes during cellular activation.

    Purpose of the Study:

    • To investigate the ability of antibiotics to enter human PMNLs during an in vitro model of infection.
    • To determine if phagocytosis or cell activation influences the uptake of specific antibiotics.
    • To explore the underlying transport mechanisms involved in antibiotic entry into phagocytes.

    Main Methods:

    • An in vitro model using human PMNLs was established.
    • Cells were incubated with ingestible particles (zymosan) or phorbol myristate acetate (PMA) to induce phagocytosis/activation.
    • Radiolabeled antibiotics (clindamycin, penicillin, erythromycin) and adenosine were added, and uptake was quantified using velocity-gradient centrifugation.

    Main Results:

    • Phagocytosis significantly enhanced clindamycin uptake by PMNLs, increasing the cellular:extracellular (C/E) ratio.
    • Penicillin entry remained unaffected, while erythromycin uptake slightly decreased post-phagocytosis.
    • Clindamycin uptake was found to be mediated by the nucleoside transport system, as evidenced by stimulated adenosine uptake, which was inhibited by clindamycin.

    Conclusions:

    • Phagocytosis markedly augments clindamycin uptake into PMNLs through stimulation of the nucleoside transport system.
    • This represents a previously undescribed significant stimulation of a membrane transport system by the process of phagocytosis.
    • The findings have implications for antibiotic efficacy against intracellular pathogens residing within phagocytes.

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