Comparative analysis of CD137 and LPS effects on monocyte activation, survival, and proliferation.

CD137 (ILA/4-1BB), a member of the TNF receptor family, regulates activation, survival and proliferation of primary human monocytes. Here we compare the activities of lipopolysaccharide (LPS), a classical and potent monocyte activator to that of CD137. LPS is a more potent activator of monocytes, as evidenced by a stronger induction of the proinflammatory cytokine IL-8. However, CD137 could further increase maximal cytokine induction by LPS, which points to separate signaling pathways for LPS and CD137. Also, expression of myc was only induced by the combination of CD137 and LPS. Expression of macrophage colony-stimulating factor is induced more potently by CD137, but an additive effect is obtained by the combination of CD137 and LPS. Monocyte/macrophage survival and proliferation is only induced by CD137. LPS counteracts both activities of CD137 via activation induced cell death. While LPS has a role in activation of monocytes in innate immunity, the CD137 receptor/ligand system seems to deliver an activating signal to monocyte in acquired immunity.