Migratory responses of polymorphonuclear leukocytes to kinin peptides.
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 B(2) receptor agonist FR190997 as well as with des-Arg(9)-bradykinin and des-Arg(10)-kallidin results in a concentration-dependent migration. Pretreatment of the neutrophils with the B(2) receptor antagonist HOE-140 (icatibant) inhibited the bradykinin-induced migration but not that induced by B(1) receptor agonists, whereas the B(1 )receptor antagonist des-Arg(10)HOE-140 abolished the migration elicited by des-Arg(9)-bradykinin or des-Arg(10)-kallidin but not that evoked by bradykinin. Pretreatment of the neutrophils with the leukotriene B(4) (LTB(4)) antagonist ZK158252 inhibited the LTB(4)-induced chemotaxis as well as the chemotaxis produced by bradykinin and des-Arg(10)-kallidin. An involvement of interleukin-1beta 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 B(1) and B(2) kinin receptors are involved in the migration of human neutrophils in vitro, that LTB(4) participates in the downstream pathway and that the B(1) kinin receptor seems to be expressed already under physiological conditions.
Paegelow
I
I
Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Rostock, Germany. inge.paegelow@med.uni-rostock.de
Trzeczak
S
S
Böckmann
S
S
Vietinghoff
G
G
D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007705:Kinins / Q000494:pharmacology* / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology
D007705:Kinins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin