Migratory Responses of Polymorphonuclear Leukocytes to Kinin Peptides

Abstract

The present study examines the influence of kinins on the migratory capacity of human polymorphonuclear leukocytes under in vitro conditions using the Boyden chamber technique. By means of checkerboard analysis the migration of neutrophils induced by bradykinin could be characterized as true chemotaxis. The stimulation of human neutrophils with bradykinin, with the nonpeptide B₂ receptor agonist FR190997 as well as with des-Arg⁹-bradykinin and des-Arg¹⁰-kallidin results in a concentration-dependent migration. Pretreatment of the neutrophils with the B₂ receptor antagonist HOE-140 (icatibant) inhibited the bradykinin-induced migration but not that induced by B₁ receptor agonists, whereas the B₁receptor antagonist des-Arg¹⁰HOE-140 abolished the migration elicited by des-Arg⁹-bradykinin or des-Arg¹⁰-kallidin but not that evoked by bradykinin. Pretreatment of the neutrophils with the leukotriene B₄ (LTB₄) antagonist ZK158252 inhibited the LTB₄-induced chemotaxis as well as the chemotaxis produced by bradykinin and des-Arg¹⁰-kallidin. An involvement of interleukin-1β and of the chemokine IL-8 in the bradykinin-induced migration in vitro could be excluded during the migration time of the neutrophils. In conclusion, the present study provides pharmacological evidence showing that B₁ and B₂ kinin receptors are involved in the migration of human neutrophils in vitro, that LTB₄ participates in the downstream pathway and that the B₁ kinin receptor seems to be expressed already under physiological conditions.

Comparison of kinin B1 and B2 receptor expression in neutrophils of asthmatic and non-asthmatic subjects

“…Furthermore, activation of kinin B 1 receptors has been shown to induce in vitro chemotaxis of neutrophils [21,26]. It is therefore possible that in asthmatic patients altered expression of the neutrophil kinin receptors may contribute to the migration of these cells into the airways, resulting in a neutrophilic inflammation.…”

Up-regulation of human bradykinin B1 receptor by secreted components ofPseudomonas aeruginosavia a NF-κB pathway in epithelial cells

“…Pulmonary epithelial cells are known to produce neutrophil chemotactic activity, which directs the migration from the vascular compartment to the alveolar space along chemotactic gradients (Koyama et al ., ). Neutrophil migration in inflamed tissues was found to be impaired in B1R‐deficient mice, suggesting that the active metabolite des‐Arg 9 ‐bradykinin is involved in inducing the migration of neutrophils (Araujo et al ., ; Paegelow et al ., ).…”

Bradykinin promotes migration and invasion of human immortalized trophoblasts

“…BK increases migration of endothelial cells [28], endothelial progenitor cells [29], neutrophils [30,31], lymphocytes [32], fibroblasts [33], dendritic cells [34], microglia [35], and cancer cells [36-38]. Interestingly, BK has been found to induce the formation of peripheral actin microspikes, filopodia and lamellipodia in fibroblasts and endothelial progenitor cells, indicating its relevance in determining an invasive phenotype [33].…”