• Inflamm. Res. · Nov 2004

    Antibacterial cathelicidin peptide CAP11 inhibits the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis by blocking the binding of LPS to target cells.

    • I Nagaoka, S Yomogida, H Tamura, and M Hirata.
    • Department of Host Defense and Biochemical Research, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. nagaokai@med.juntendo.ac.jp
    • Inflamm. Res. 2004 Nov 1;53(11):609-22.

    ObjectiveThe action of antibacterial cathelicidin CAP11 (cationic antibacterial polypeptide of 11 kDa) on the lipopolysaccharide (LPS)-induced suppression of neutrophil apoptosis was evaluated in vitro.MethodsHuman neutrophils (10(6) cells/ml) were incubated alone or with mononuclear cells (6 x 10(5) cells/ml) in the presence of LPS (10 ng/ml) and CAP 11 (0.1 approximately 10 microg/ml), and neutrophil apoptosis was determined.ResultsLPS suppressed neutrophil apoptosis, accompanied with the activation of NF-kappaB, phosphorylation of extracellular signal-related protein kinase (ERK), expression of Bcl-XL (an anti-apoptotic protein) and inhibition of caspase 3 activity. Interestingly, CAP11 (> 1 microg/ml) reversed the actions of LPS to trigger these changes, and induced neutrophil apoptosis (p < 0.0001). Moreover, neutralizing antibodies against Mac-1 (CD11b/CD18) and Toll-like receptor (TLR) 4 completely blocked the LPS-induced suppression of neutrophil apoptosis (p < 0.0001), suggesting a major role of Mac-1 and TLR4 in the LPS-mediated neutrophil activation. In addition, LPS activated monocytes to produce proinflammatory cytokines (IL-1beta, TNF-alpha and IL-8) and inhibited neutrophil apoptosis. Importantly, CAP11 (> 1 microg/ml) reduced the cytokine production, thereby inducing neutrophil apoptosis (p < 0.0001). Finally, CAP11 (> 1 microg/ml) strongly suppressed the LPS-binding to neutrophils and monocytes (p < 0.01).ConclusionsCAP11 is able to block the LPS-induced survival of neutrophils via the suppression of anti-apoptotic signaling in neutrophils and cytokine production from monocytes by inhibiting the binding of LPS to target cells.

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