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Infection and Immunity, December 2002, p. 6904-6910, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6904-6910.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Arginine-Rich Cationic Polypeptides Amplify Lipopolysaccharide-Induced Monocyte Activation

Herbert Bosshart1,2 and Michael Heinzelmann1*

Department of Surgery, University Hospital, 8091 Zurich,1 Research Laboratory for Calcium Metabolism, Departments of Orthopedic Surgery and Medicine, University Hospital, 8008 Zurich, Switzerland2

Received 22 July 2002/ Accepted 19 September 2002

The human neutrophil-derived cationic protein CAP37, also known as azurocidin or heparin-binding protein, enhances the lipopolysaccharide (LPS)-induced release of tumor necrosis factor alpha (TNF-{alpha}) in isolated human monocytes. We measured the release of the proinflammatory cytokine interleukin-8 (IL-8) in human whole blood and found that in addition to CAP37, other arginine-rich cationic polypeptides, such as the small structurally related protamines, enhance LPS-induced monocyte activation. As CAP37 and protamines share high levels of arginine content, we tested different synthetic poly-L-amino acids and found that poly-L-arginine, and to a lesser extent poly-L-lysine, increased IL-8 production in LPS-stimulated human whole blood. Protamine-enhanced LPS responses remained unaffected by the presence of free L-arginine or L-lysine, indicating that basic polypeptides but not basic amino acids act synergistically with LPS. In agreement with observations previously reported for CAP37, the LPS-enhancing effect of poly-L-arginine was completely abolished upon antibody blockade of the human LPS receptor, CD14. Protamines, either immobilized or in solution, bound LPS specifically. Poly-L-arginines, protamines, and CAP37 were equally effective in inhibiting binding of LPS to immobilized L-arginines. Taken together, our results suggest a CD14-dependent mechanism by which arginine-rich cationic proteins modulate LPS-induced monocyte activation and support the prediction that other strongly basic proteins could act as amplifiers of LPS responses.

* Corresponding author. Mailing address: Department of Surgery, University Hospital, Ramistrasse 100, CH-8091 Zurich, Switzerland. Phone: 41 1 255 1111. Fax: 41 1 255 4198. E-mail: mheinzelmann{at}bluewin.ch.

Editor: S. H. E. Kaufmann

Infection and Immunity, December 2002, p. 6904-6910, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6904-6910.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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