Abstract
BackgroundKinins are short peptides with a wide range of proinflammatory properties that are generated from kininogens in the so-called kallikrein-kinin system. Kinins exert their biological activities through stimulation of two distinct receptor subtypes, the kinin or bradykinin B1 and B2 receptors (B1R, B2R). Acute challenge models have implicated B1R and B2R in the pathogenesis of sepsis. However, their role in the host response during sepsis originating from the lung is not known.ResultsTo determine the role of B1R and B2R in pneumonia-derived sepsis, B1R/B2R-deficient mice and wild-type mice treated with the B1R antagonist R-715 or the B2R antagonist HOE-140 were studied after infection with the common gram-negative pathogen Klebsiella pneumoniae via the airways. Neither B1R/B2R deficiency nor B1R or B2R inhibition influenced bacterial growth at the primary site of infection or dissemination to distant body sites. In addition, B1R/B2R deficiency or inhibition did not impact local or systemic inflammatory responses during Klebsiella induced pneumosepsis.ConclusionsThese data argue against an important role for kinins in the host response to pneumonia-derived sepsis caused by a clinically relevant pathogen.
Highlights
Kinins are short peptides with a wide range of proinflammatory properties that are generated from kininogens in the so-called kallikrein-kinin system
Kinins are released by cleavage of high molecular weight kininogens (HMWK) by plasma kallikrein (PK), and by cleavage of low molecular weight kininogen by tissue kallikrein; the name kallikrein-kinin system (KKS)
We investigated bradykinin B1/B2 receptor (B1R/B2R)-deficient mice and wild-type mice treated with bradykinin receptor antagonists in an established model of respiratory tract infection with the common gram-negative pathogen Klebsiella (K.) pneumoniae resulting in a gradually growing bacterial load in the lungs with subsequent dissemination to distant body sites and sepsis
Summary
Kinins are short peptides with a wide range of proinflammatory properties that are generated from kininogens in the so-called kallikrein-kinin system Kinins exert their biological activities through stimulation of two distinct receptor subtypes, the kinin or bradykinin B1 and B2 receptors (B1R, B2R). Kinins are released by cleavage of high molecular weight kininogens (HMWK) by plasma kallikrein (PK), and by cleavage of low molecular weight kininogen by tissue kallikrein; the name kallikrein-kinin system (KKS). They exert their biological activities through stimulation of two distinct receptor subtypes, the kinin or bradykinin B1 and B2 receptors (B1R, B2R) [1, 2]. Kinins are end-products of the contact system, which apart from PK and HMWK is composed of coagulation factors XI (FXI) and FXII [2, 3].
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