Engagement of CD11b and CD11c beta 2 integrin by antibodies or soluble CD23 induces IL-1 beta production on primary human monocytes through mitogen-activated protein kinase-dependent pathways

beta 2 integrins are involved in the recruitment of leukocytes to inflammat ory sites and in cellular activation. We demonstrate that ligation of CD11b (Mac-1, CR3) or CD11c (p150, CR4) alpha chains of beta 2 integrins by mAbs or soluble chimeric CD23 (sCD23) on human freshly isolated monocytes rapid ly stimulates high levels of interleukin-1 beta production. This induction takes place at the transcriptional level and is regulated by members of the mitogen-activated protein kinase (MAPK) family. Indeed, stimulation of mon ocytes through engagement of CD11b or CD11c results in the phosphorylation and activation of ERK1, ERK2, and p38/SAPK2 MAP kinases, U0126, a potent in hibitor of the upstream activator of ERK1/2, ie, MEK1/2, suppresses IL-1 be ta messenger RNA (mRNA) expression in a dose-dependent fashion, showing the implication of this pathway in the transcriptional control of IL-1 beta pr oduction. On the other hand, inhibition of p38 by SB203580 indicates that t his MAPK is involved in the control of IL-1 beta production at both transcr iptional and translational levels. Together these data demonstrate that lig ation of CD11b and CD11c beta 2 integrins by mAbs or sCD23 fusion proteins triggers the activation of 2 distinct MAPK signaling pathways that cooperat e in controlling IL-1 beta synthesis at different levels. (C) 2000 by The A merican Society of Hematology.