Effect of GM-CSF on HIV-1 replication in monocytes/macrophages in vivo and in vitro: a review.

Cells of macrophage lineage constitute the main cellular target of Human Immunodeficiency Virus type 1 (HIV-1). Replication of HIV-1 in monocyte/macrophages is generally augmented by factors promoting their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key regular of the differentiation of cells of macrophage lineage. The effects of GM-CSF on HIV-1 replication in vitro are still controversial. Most of the published studies suggest that GM-CSF upregulates HIV-1 expression in both primary cultured macrophages and promonocytic cell lines. There have also been reports demonstrating that GM-CSF does not affect HIV-1 replication in cells of macrophage lineage or that GM-CSF can actually suppress HIV-1 expression. In vivo, GM-CSF administrated to HIV-positive patients at any stage of disease, without any antiretroviral therapy, appears to increase HIV-1 activity. The possible mechanism by which GM-CSF might affect HIV-1 replication in macrophages remains unclear.

Eosinophil-mediated killing of Haemonchus contortus larvae: effect of eosinophil activation and role of antibody, complement and interleukin-5.

Eosinophils have previously been shown to accumulate around the tissue invasive (L3) stage of sheep gastrointestinal parasites in vivo. In this study, eosinophils obtained from mammary washes of sheep, were shown to immobilize and kill H. contortus larvae in vitro in the presence of antibody specific against a defined L3 surface antigen. Eosinophils obtained from sheep primed by repeated infusion of H. contortus larvae were more effective than eosinophils obtained after a single infusion of parasite extract in Fasciola hepatica infected ewes suggesting the former were activated in vivo. The level of larval immobilization in the presence of antibody was significantly increased when complement was added to cultures containing activated eosinophils. The addition of interleukin-5 to larval cultures containing antibody and complement resulted in a significant increase in larval immobilization with unactivated eosinophils suggesting that eosinophil effector function is enhanced following priming with this cytokine. Ultrastructural analysis of the eosinophil/larvae interaction at 6 h of incubation revealed degranulation of adhering eosinophils onto the surface of larvae. By 24 h of incubation, many larvae showed signs of damage and most eosinophils had degenerated. These results suggest that eosinophil-mediated killing may be an effector mechanism for the elimination of L3 H. contortus larvae in immune sheep.