Influence of kinin peptides on monocyte-endothelial cell adhesion

Abstract

Adhesion of leukocytes to vascular endothelium in response to proinflammatory mediators is an important component of the overall inflammatory reaction. In the current work, we used a retinoic acid-differentiated human promonocytic cell line, U937 and a human microvascular endothelial cell line, HMEC-1 to analyze the effect of the potent pro-inflammatory bradykinin-related peptides (kinins) on cell adhesion. Bradykinin (BK) and kinin metabolites without the C-terminal arginine residue enhanced adhesion of the monocyte-like cells to fibronectin and to the HMEC-1 cells. Expression of adhesion proteins on the surface of both cell types was altered by the kinin peptides. In the monocyte-like cells, expression of CD11b, a subunit of Mac-1 integrin, was significantly increased whilst in the endothelial cells, a strong increase in the production of intercellular adhesion molecule 1 (ICAM-1) was observed. The positive bradykinin-induced effect on the cell-cell interaction was reversed by a carboxypeptidase inhibitor (MGTA), hence we suspected a significant role of the des-Arg kinin metabolites, which acted through the kinin receptor type 1. Indeed, the expression of this receptor was up-regulated not only by agonists but also by interferon-γ and bradykinin. Kinin peptides also regulated signal transducer and activator of transcription proteins (STATs) activated by cytokines. Taken together, the above observations support our hypothesis that kinins stimulate monocyte adhesion to the vessel wall, especially during pathological states of the circulatory system accompanied by proinflammatory cytokine release.

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

“…Ju et al (2000) reported an increased pSTAT3 level in bovine aortic endothelial cells 5 minutes after B2R activation. Similar results, with a maximal response after 15 minutes of BK-induction, were obtained in studies performed on a human microvascular endothelial cell line (Guevara-Lora et al, 2014). In this study, we demonstrated enhanced STAT3 phosphorylation after the 15-min treatment with BK, but it was significantly reduced after the co-stimulation with BK and SUM (Fig.…”

“…These observations correlate with the finding discussed above and corroborate the protective role of D2R agonists in the inhibition of pro-inflammatory processes induced by BK in the vascular system. However, additional studies analyzing the B1R involvement should be conducted, since this receptor has a great importance for leukocyte adhesiveness during chronic inflammation (Figueroa et al, 2015) and is concurrently able to regulate STAT3 activation in monocytes (Guevara-Lora et al, 2014). Although the influence of D2R on the regulation of STAT3 phosphorylation has been reported (Kim et al, 2010;Qiu et al, 2016), our study showed no significant changes in the level of this parameter.…”

“…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.…”

“…Activation of B2R is particularly essential for the regulation of vascular tone and permeability, which control arterial pressure and cell migration through microvessel walls (Ishihara et al, 2002;Su, 2015). BK has been shown to increase monocyte adhesion to endothelial cells by enhancement of the expression of adhesion proteins, ICAM-1 and macrophage-1 antigen (Mac-1, CD11b/CD18) respectively, in human endothelial cells and monocytes (Guevara-Lora et al, 2014). In contrast, a reduced amount of rolling and adherent leukocytes was observed in mice with induced global cerebral ischemia treated with a B2R antagonist (Lehmberg et al, 2003).…”

The Implications of Angiotensin-Converting Enzymes and Their Modulators in Neurodegenerative Disorders: Current and Future Perspectives

“…In pathological conditions, a rise in the level of bradykinin in the respiratory system causes acute respiratory distress syndrome (ARDS, a form of acute lung injury), dry cough, inflammation, and apoptosis via release of proinflammatory mediators such as cytokines (TNF-α and interferon-γ) and chemokines, that is, CXCL 5 . − Bradykinin has pleiotropic actions, that is, decreased blood pressure, increased vascular permeability, and promotion of classical symptoms of inflammation such as vasodilation, hyperthermia, edema, and pain (warning signal). In addition, it has beneficial effects, that is, potent antithrombogenic, antiproliferative, and antifibrogenic effects .…”