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The Journal of Immunology, 2007, 178, 8046-8052
Copyright © 2007 by The American Association of Immunologists, Inc.

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Human Neutrophil Defensins Increase Neutrophil Uptake of Influenza A Virus and Bacteria and Modify Virus-Induced Respiratory Burst Responses

Tesfaldet Tecle*, Mitchell R. White*, Don Gantz{dagger}, Erika C. Crouch{ddagger} and Kevan L. Hartshorn1,*

* Department of Medicine, Boston University School of Medicine and {dagger} Department of Biophysics, Boston, MA 02118; and {ddagger} Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Human neutrophil peptides (HNPs) are released from granules of neutrophils in response to various activating stimuli and they participate in the killing of bacteria and the stimulation of various inflammatory responses. HNPs also inhibit infectivity of enveloped viruses, including influenza A virus (IAV). In this study, we demonstrate that HNPs increase the uptake of IAV and bacteria by neutrophils. The dimeric HNPs also induced aggregation of IAV and bacterial particles, which may, in part, explain their ability to increase uptake. HNPs did not increase neutrophil respiratory burst responses to IAV. We have recently demonstrated direct interactions of HNPs with surfactant protein D (SP-D), another important effector of innate immunity and antimicrobial host defense. Although HNPs did not alter SP-D-dependent uptake of IAV, they counteracted the ability of SP-D to increase IAV-induced neutrophil H2O2 generation. Our studies reveal previously unappreciated functional effects of HNPs, expand our understanding of the antiviral properties of HNPs, and suggest important interactions between collectins and HNPs in the host response to viruses and bacteria.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Address correspondence and reprint requests to Dr. Kevan L. Hartshorn, Boston University School of Medicine, Evans Biomedical Research Center 414, 650 Albany Street, Boston, MA 02118. E-mail address: khartsho{at}bu.edu

2 Abbreviations used in this paper: IAV, influenza A virus; HNP, human neutrophil peptide; SP-D, surfactant protein D; HD5, human defensin 5; HBD, human beta-defensin; RhSP-D, recombinant human SP-D; BALF, bronchoalveolar lavage fluid.




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