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 activatio n, survival and proliferation of primary human monocytes, Here we compare t he 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, Ho wever, CD137 could further increase maximal cytokine induction by LPS, whic h 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, bu t an additive effect is obtained by the combination of CD137 and LPS. Monoc yte/macrophage survival and proliferation is only induced by CD137. LPS cou nteracts both activities of CD137 via activation induced cell death. While LPS has a role in activation of monocytes in innate immunity, the CD137 rec eptor/ligand system seems to deliver an activating signal to monocyte in ac quired immunity. (C) 2000 Academic Press.