Bradykinin and des-Arg¹⁰-kallidin enhance the adhesion of polymorphonuclear leukocytes to extracellular matrix proteins and endothelial cells

Abstract

Bradykinin-related peptides (kinins) are well known to contribute to leukocyte recruitment to infl ammatory foci; however, a role of these universal pro-infl ammatory mediators in the fi rst step of this process, i.e. the leukocyte adhesion to endothelial cells, is not well understood. In this work we found that bradykinin and des-Arg 10 -kallidin enhance the adhesion of polymorphonuclear bloods cells (PMN) to fi brinogen and fi bronectin. Also, the PMN adherence to endothelial cells of HMEC-1 line strongly increased after stimulation by kinins, particularly des-Arg 10 -kallidin, or when PMN were costimulated with bradykinin and interleukin-1 β . These effects were attenuated after PMN treatment with a specifi c inhibitor of carboxypeptidases, which convert kinins to their des-Arg metabolites. The kinin peptides were also able to change the Mac-1 integrin expression on the PMN surface. These results suggest a regulatory effect of kinins on leukocyte adhesion to endothelial wall, providing new aspects of the leukocyte infi ltration into infl amed tissues.

Bradykinin B2 receptor and dopamine D2 receptor cooperatively contribute to the regulation of neutrophil adhesion to endothelial cells*

“…The analyzed immortalized endothelial cell line isolated from the human umbilical vein expresses both receptors endogenously, confirming earlier reports of the expression of these receptors in endothelial cells (Zarei et al, 2006;Terzuoli et al, 2014). In accordance with previous reports (Schuschke et al, 2001;Guevara-Lora et al, 2011), the current study indicated that BK increased the PMN adhesion to endothelial cells, with a maximal response observed after 6 hours of cell incubation (Fig. 1A).…”

“…Isolated PMN were suspended in RPMI-1640 medium and loaded with Cell Tracker Red CMTPX in RPMI for 30 min at 37°C, following the manufacturer's instructions, and then placed on a monolayer of endothelial cells stimulated as described below. Detailed description of the cell adhesion analysis was provided elsewhere (Guevara-Lora et al, 2011).…”

“…The fact that kinin peptides induce leukocyte adhesion to endothelial cells is well known (Guevara-Lora et al, 2011;Guevara-Lora et al, 2014;Figueroa et al, 2015). In order to investigate the effect of D2R activation on BK-induced adhesion, endothelial cells were stimulated with 100 nM BK and 100 nM SUM and co-stimulated with both agonists at the same concentration at different incubation time: 6, 12, and 24 hours.…”

“…Additional substances that accumulate at the injury site during inflammation, such as kinin peptides play an important role in leukocyte adhesion (Guevara-Lora et al, 2011;Figueroa et al, 2015). Kinins, including bradykinin (BK), kallidin, and their metabolites without arginine at the C-end, are well known pro-inflammatory peptides, and are recognized by specific receptorsbradykinin receptor type 1 and type 2 (B1R and B2R, respectively).…”

Influence of kinin peptides on monocyte-endothelial cell adhesion

“…Involvement of kinin receptors in chemotaxis, cell migration, and trafficking was proposed [Koyama et al, ; McLean et al, ; Sainz et al, ; Lu et al, ; Yang et al, ]. We have recently reported that the adhesion of polymorphonuclear leukocytes (PMN) can be enhanced by kinin peptides [Guevara‐Lora et al, ]. PMN adhesion to the endothelial cells was regulated by BK and, even more remarkably, by B1R agonists.…”