Ligation of CD11b and CD11c β2 integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β production in primary …

R Rezzonico, V Imbert… - Blood, The Journal of …, 2001 - ashpublications.org
R Rezzonico, V Imbert, R Chicheportiche, JM Dayer
Blood, The Journal of the American Society of Hematology, 2001ashpublications.org
Chemokines and adhesion molecules such as integrins play a major part in the trafficking,
extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated
the effects of β2 integrin engagement on chemokine production by freshly isolated human
monocytes. We found that ligation of CD11b or CD11c but not CD11a α chains of β2
integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced
transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1α, and …
Abstract
Chemokines and adhesion molecules such as integrins play a major part in the trafficking, extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated the effects of β2 integrin engagement on chemokine production by freshly isolated human monocytes. We found that ligation of CD11b or CD11c but not CD11a α chains of β2 integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1α, and MIP-1β. Because the promoters of these chemokine genes contain κB binding sites, we assessed the possible role of nuclear factor–κB (NF-κB) in controlling induction of the genes through β2 integrin engagement. Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-κB. Activation of NF-κB was accompanied by degradation of its cytosolic inhibitor IκB-α. Blockade of depletion of IκB-α by proteasome inhibitors (proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-κB DNA-binding activity and expression of MIP-1α and MIP-1β messenger RNA induced by β2 integrin ligation. These results suggest that triggering of CD11b or CD11c β2 integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-κB and subsequent secretion of MIP-1α and MIP-1β that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response.
ashpublications.org