Production of the effector molecule thymidine by human lung alveolar macrophages

A, Vercammen-Grandjean; Arnould, Roland; Libert, Anita; Ewalenko, Patricia; Lejeune, Ferdy J.

doi:10.1016/0277-5379(84)90148-2

Cited by 7 publications

(1 citation statement)

References 14 publications

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“…Murine (22,23) and human (24) macrophages have been reported to lack thymidine kinase activity . These cells, in fact, release deoxypyrimidines extracellularly, an activity that has been proposed to modulate lymphocyte function (22)(23)(24). It is not surprising that a cell no longer programmed to synthesize DNA has reduced requirements for deoxynucleoside salvage.…”

Section: Discussionmentioning

confidence: 99%

Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages.

Richman

Kornbluth

Carson

1987

The Journal of Experimental Medicine

142

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Primary human monocyte-derived macrophages (MDM) were shown to have diminished deoxynucleoside kinase activities compared to T lymphoblasts, and a reduced ability to phosphorylate dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity. These drugs, azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyadenosine (ddA), which are potent anti-HIV agents in CD4 lymphocytes, did not inhibit HIV replication in MDM, even at concentrations of 100 microM. This drug concentration of AZT is approximately 100-fold higher than the levels attained in the serum of treated patients and the levels required to inhibit HIV replication in lymphocytes. These observations may explain the failure of AZT therapy to clear viremia, consistent with the presence of a drug-resistant reservoir of infected cells in vivo. New therapeutic approaches to inhibit the replication of HIV in MDM may be needed.

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