Granulocyte–macrophage colony‐stimulating factor regulates cytokine production in cultured macrophages through CD14‐dependent and ‐independent mechanisms

Abstract

SUMMARYGranulocyte±macrophage colony-stimulating factor (GM-CSF) has multiple effects on the antigen phenotype and function of macrophages. In this study we investigated the effect of GM-CSF on cytokine production by macrophages. We found that GM-CSF may modify the tumour necrosis factor-a (TNF-a) and interleukin-6 (IL-6) response to lipopolysaccharide (LPS) through two different mechanisms. Relatively early in culture, GM-CSF increases the amount of cytokines synthesized by responding cells; this effect appears to be unrelated to modulation of CD14 expression and LPS-binding capacity. After prolonged incubation, GM-CSF up-regulates both CD14 expression and LPS-binding capacity, and the frequency of cytokine-producing cells. Release of CD14 in the culture supernatant was decreased in the presence of GM-CSF, suggesting that a reduced shedding was responsible for the effect of GM-CSF on CD14 expression. Enhancement of cytokine production was also observed in GM-CSF-treated macrophages after stimulation by phorbol 12-myristate 13-acetate (PMA), thus indicating that GM-CSF affects both CD14-dependent and -independent cytokine production. Finally, GM-CSF did not modulate the LPS-and PMA-induced production of IL-10 and IL-12. We conclude that GM-CSF may play a role in manipulating the activation-induced expression of pro-in¯ammatory cytokines by macrophages. Enhanced production of these cytokines could play an important role in the pathogenesis of Gram-negative septic shock syndrome and in defence against infectious agents.

Phagocytosis and Killing of Bacteria by Professional Phagocytes and Dendritic Cells

“…In this report, the levels of phagocytosis as well as the killing of bacteria by both professional phagocytes and MDM were compared. As expected, MDM ingested the highest number of pathogens per cell, and their ability to kill bacteria increased in the presence of PMA as an additional stimulus (4,6). The phagocytotic activity of imDC was equivalent to that of PMN and monocytes, while that of maDC was significantly lower.…”

A role for BLyS in the activation of innate immune cells

“…Even though M-CSF and GM-CSF maintain monocyte survival and support monocyte differentiation, they are not able to induce detectable secretion of TNF-␣, or IL-6 protein in monocytes by themselves. 49,50 Thus BLySstimulated monocyte secretion of IL-6, TNF-␣, and IL-1␤ did not simply reflect higher monocyte viability, indicating that BLyS is uniquely capable of activating monocytes to produce the proinflammatory cytokines.…”

Contribution of TRPV1 to Microglia-Derived IL-6 and NFκB Translocation with Elevated Hydrostatic Pressure

“…13 We further identified the ubiquitin-proteasome pathway and activation of the transcription factor nuclear factor kappa B (NFB), which are responsible for the production of IL-6 by astrocytes, microglia, and macrophages in other systems, [27][28][29][30][31][32][33][34][35][36][37] as components of the pressure-induced release of IL-6. 14 In other systems, the influx of extracellular Ca 2ϩ can induce IL-6 production through the activation of NFB, 38 -41 including that induced by cellular stretch.…”