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Related Experiment Videos

Cyclic nucleotides regulate the morphologic alterations required for chemotaxis in monocytes.

C G Stephens, R Snyderman

    Journal of Immunology (Baltimore, Md. : 1950)
    |March 1, 1982
    PubMed
    Summary
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    Chemoattractants rapidly polarize human monocytes, a process modulated by cyclic nucleotides. Agents affecting cyclic guanosine monophosphate (cGMP) enhance this response, while those increasing cyclic adenosine monophosphate (cAMP) inhibit it.

    Area of Science:

    • Cell Biology
    • Immunology
    • Biochemistry

    Background:

    • Human monocytes exhibit a characteristic polarization response to chemoattractants, involving a shape change from round to a motile configuration.
    • This initial morphologic change is crucial for monocyte function and migration.

    Purpose of the Study:

    • To investigate the signaling pathways involved in monocyte polarization induced by chemoattractants.
    • To determine the role of cyclic nucleotides, specifically cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), in modulating this response.

    Main Methods:

    • Monocyte polarization was induced using chemoattractants and various pharmacologic agents in vitro.
    • The requirement for extracellular calcium (Ca++) was assessed.
    • The effects of agents influencing cAMP and cGMP levels on monocyte polarization and chemotaxis were evaluated.

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    Main Results:

    • Chemoattractants induced rapid and sustained monocyte polarization, independent of extracellular Ca++ but with slower kinetics in its absence.
    • Pharmacologic agents like phenylephrine, serotonin, and ascorbate also induced polarization, but it was unsustained and Ca++-dependent.
    • Agents that increase cGMP (e.g., muscarinic agonists) enhanced chemoattractant-induced polarization, while agents that increase cAMP (e.g., histamine, isoproterenol) inhibited it.

    Conclusions:

    • Monocyte polarization to chemoattractants involves a pathway that shares similarities with agents enhancing cGMP and inhibiting adenylate cyclase.
    • Both the initial polarization and sustained motility of monocytes are significantly modulated by intracellular cyclic nucleotide levels.
    • Understanding these pathways offers insights into immune cell function and potential therapeutic targets.