Human blood dendritic cells: binding to vascular endothelium and expression of adhesion molecules

Abstract

SUMMARYTo investigate the binding properties of dendritic cells (DC) to vascular endothelium, a comparative analysis was undertaken of DC, monocytes and lymphocytes isolated from the blood of 25 healthy subjects using monolayers of human umbilical vein endothelial cells as the adherence substrate. More blood DC (mean 24% adherence) were adherent to endothelial monolayers than monocytes (mean 18%; P < 0 . 001) and lymphocytes (mean 12%; P < 0 . 001). When the monolayers were pretreated with tumour necrosis factor-alpha (TNF-a) all leucocyte populations exhibited an increased attachment, but there was still greater binding of DC (mean 37% adherence) in comparison with monocytes (mean 23%; P < 0 . 001) and lymphocytes (mean 18%; P < 0 . 001). Flow cytometric analysis revealed that in relation to monocytes and lymphocytes the DC had a higher surface expression of the adhesion molecules CD11a (P < 0 . 05), CD11c (P < 0 . 005) and CD54 (P < 0 . 005) but a lower prevalence of cells bearing CD49d (mean 38%; P < 0 . 05) and the homing receptor CD62L (mean 14%; P < 0 . 001). CD1a was present on 22% of DC and virtually absent from the surface of monocytes and lymphocytes. The intensity of expression of the b 1 -integrins, CD49c, CD49d and CD49e was greater on DC than lymphocytes and monocytes (P < 0 . 05). Antibody blocking studies demonstrated that DC binding to untreated and TNF-a-treated endothelium was dependent upon the expression of CD11a, CD18 and CD49d, and the simultaneous application of anti-CD18 and anti-CD49d antibodies produced an approximate 70% inhibition of adhesion (P < 0 . 001). Thus, the expression of both b 1 -and b 2 -integrins contributes to the adhesive interaction between DC and endothelium.

Ligation of the FcRγ Chain-Associated Human Osteoclast-Associated Receptor Enhances the Proinflammatory Responses of Human Monocytes and Neutrophils

“…This cleavage was also strongly induced by LPS and R-848 but only weakly by Pam 3 Cys. CD62L mediates leukocyte rolling on activated endothelium in inflamed tissues and lymphocyte homing to high endothelial venules of peripheral lymphoid tissue (30). Thus, activation of myeloid cells via hOSCAR interaction with its ligand may by itself be sufficient to set up a gradient of recruitment of immune cells to the site of interaction.…”

Material-driven fibronectin fibrillogenesis to engineer cell function.

“…In particular, eight of the twenty-four known integrins bind RGD peptide (Barczyk et al, 2010;Hynes, 2002), several of which are expressed by DCs, including the α v integrins (Ammon et al, 2000;Brown et al, 1997;Dubey et al, 1995;Maestroni & Mazzola, 2003;Puig-Kroger et al, 2000;Sung et al, 2006). The RGD integrin binding motif is present in several ECM proteins including FN and VN (Dickinson et al, 1994;Humphries et al, 2006), and is one of the motives that has been investigated with numerous cell types (Fittkau et al, 2005;Mann et al, 2001;Schaffner & Dard, 2003).…”

“…It has been shown that DCs interactions with various biomaterials modulate DCs functions (Babensee, 2008;Jones, 2008) and that DCs express multiple integrins (Ammon et al, 2000;Brown et al, 1997;Dalgaard et al, 2005;Dubey et al, 1995;Hamakawa et al, 2006;Lu et al, 1995;Sung et al, 2006), but there are surprisingly few investigations into the effects of integrin binding to ECM proteins on DCs maturation and only a few investigations have begun to elucidate the mechanisms involved into the modulation of DC functions (Acharya et al, 2009;Acharya et al, 2008;Acharya et al, 2011;Brand et al, 1998;Kohl et al, 2007;Shankar et al, 2010). DCs have been cultured on surfaces presenting a uniform gradient of the integrin targeting RGD peptide and demonstrate the utility of the surface density gradient platform as a high-throughput method to investigate RGD densitydependent DCs adhesive responses (Acharya et al, 2010).…”

“…It has been demonstrated that integrins can guide cell functions such as proliferation and differentiation (Hynes, 2002;Miyamoto et al, 1995). DCs express multiple integrins (α X β 2 , α L β 2 , α M β 2 , α E β 7 , α 2 β 1 , α 1 β 1 , α 4 β 1 , α 4 β 7 , α 3 β 1 , α 7 β 1 , α 6 β 4 , as well as the RGD-peptide binding integrins, α V β 8 , α V β 6 , α V β 3 , α V β 5 , α 5 β 1 and α IIb β 3 ) (Ammon et al, 2000;Brown et al, 1997;Dalgaard et al, 2005;Dubey et al, 1995;Hamakawa et al, 2006;J. Lo & Clare-Salzler, 2006;Sung et al, 2006).…”

“…Eight of the twenty-four known integrins bind RGD peptide (Barczyk et al, 2010;Hynes, 2002), several of which are expressed by DCs, including the α v integrins (Ammon et al, 2000;Brown et al, 1997;Dalgaard et al, 2005;Li et al, 2006;Lu et al, 1995;Sung et al, 2006). Only a few investigations have begun to elucidate the mechanisms involved in the modulation of DC functions (Acharya et al, 2009;Acharya et al, 2008;Brand et al, 1998;Kohl et al, 2007;Shankar et al, 2010).…”