Human Upper Airway Structural Cell-derived Cytokines Support Human Peripheral Blood Monocyte Survival: A Potential Mechanism for Monocyte/Macrophage Accumulation in the Tissue

A central feature of chronic airway inflammation is accumulation of monocyte/macrophages in the tissue. It is well known that circulating monocytes are short-lived cells whereas tissue macrophages are longer-lived cells. One mechanism that may account for accumulation of inflammatory cells includes enhanced survival and/or differentiation of these cells. Recent studies imply that signals released by tissue structural cells may be crucial in these events. To investigate this notion, human blood monocytes were cultured with either culture medium alone as a control, human nasal epithelial cell-conditioned medium (EpCM), or fibroblast-conditioned medium (FCM) for more than 1 wk. Survival of monocytes in medium alone was 17% at day 7, whereas survival of those cultured with 50% of EpCM or FCM was 62% and 64%, respectively. The effect of EpCM and FCM was dose dependent. Preincubation of either conditioned medium (CM) with an antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF) or an antibody against macrophage colony-stimulating factor (M-CSF) resulted in a partial abrogation of the survival-enhancing effect, to an average of 50% and 30%, respectively. Complete inhibition was obtained by preincubation of the CM with a combination of both antibodies. The effect of CM represented true survival because CM only induced a low profile of 3Hthymidine incorporation and, furthermore, less than 0.3% of the cells cultured with CM underwent DNA synthesis as assessed by autoradiography. In addition, ultrastructural observations demonstrated that most monocytes cultured with either CM but not with control culture medium assumed ultrastructural features of macrophages by day 8 of culture.(ABSTRACT TRUNCATED AT 250 WORDS)