HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hashimoto, Y. Articles by Nakanishi, Y. Search for Related Content PubMed PubMed Citation Articles by Hashimoto, Y. Articles by Nakanishi, Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene

Evidence for Phagocytosis of Influenza Virus-Infected, Apoptotic Cells by Neutrophils and Macrophages in Mice¹

Yumi Hashimoto^*, Takeshi Moki, Takenori Takizawa, Akiko Shiratsuchi^*, and Yoshinobu Nakanishi^2,*,

^* Graduate School of Medical Science and Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan; and Department of Virology, Toyama Institute of Health, Toyama, Japan

Influenza virus-infected cells undergo apoptosis and become susceptible to phagocytosis by macrophages in vitro, and this leads to the propagation of the virus being inhibited. We previously showed that inhibitors of phagocytosis increased the rate of mortality among influenza virus-infected mice. However, the mode of the phagocytosis of influenza virus-infected cells in vivo has not been investigated. We, in this study, assessed this issue by histochemically analyzing bronchoalveolar lavage cells and lung tissue obtained from C57BL/6 mice infected with influenza A/WSN (H1N1) virus. Both neutrophils and macrophages accumulated in the lung soon after the viral challenge, and either type of cell was capable of phagocytosing influenza virus-infected, apoptotic cells. Changes in the level of phagocytosis and the amount of virus in lung tissue roughly correlated with each other. Furthermore, alveolar macrophages prepared from influenza virus-infected mice showed greater phagocytic activity than those from uninfected mice. The phagocytic activity of macrophages was stimulated in vitro by a heat-labile substance(s) released from influenza virus-infected cells undergoing apoptosis. These results suggested that the level of phagocytosis is augmented both quantitatively and qualitatively in the lung of influenza virus-infected animals so that infected cells are effectively eliminated. Finally, lack of TLR4 caused an increase in the rate of mortality among influenza virus-challenged mice and a decrease in the level of phagocytosis of apoptotic cells in the lung. TLR4 could thus play an important role in the host defense against influenza by positively regulating the phagocytic elimination of infected cells.

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 This study was supported by a grant from the Japan Research Foundation for Clinical Pharmacology, and in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grants 16570112 and 18570123).

² Address correspondence and reprint requests to Dr. Yoshinobu Nakanishi, Graduate School of Medical Science, Kanazawa University, Shizenken, Kakuma-machi, Kanazawa,Ishikawa 920-1192, Japan. E-mail address: nakanaka{at}kenroku.kanazawa-u.ac.jp

³ Abbreviations used in this paper: WSN, influenza A/WSN (H1N1) virus; AM, alveolar macrophage; ISNT, in situ nick translation; z-VAD-fmk, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone.

This article has been cited by other articles:

				M. D. Tate, Y.-M. Deng, J. E. Jones, G. P. Anderson, A. G. Brooks, and P. C. Reading Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection J. Immunol., December 1, 2009; 183(11): 7441 - 7450. [Abstract] [Full Text] [PDF]

				J. McGill, J. W. Heusel, and K. L. Legge Innate immune control and regulation of influenza virus infections J. Leukoc. Biol., October 1, 2009; 86(4): 803 - 812. [Abstract] [Full Text] [PDF]

				M. Doss, M. R. White, T. Tecle, D. Gantz, E. C. Crouch, G. Jung, P. Ruchala, A. J. Waring, R. I. Lehrer, and K. L. Hartshorn Interactions of {alpha}-, {beta}-, and {theta}-Defensins with Influenza A Virus and Surfactant Protein D J. Immunol., June 15, 2009; 182(12): 7878 - 7887. [Abstract] [Full Text] [PDF]

				H. Fujisawa Neutrophils Play an Essential Role in Cooperation with Antibody in both Protection against and Recovery from Pulmonary Infection with Influenza Virus in Mice J. Virol., March 15, 2008; 82(6): 2772 - 2783. [Abstract] [Full Text] [PDF]

				S. Kohyama, S. Ohno, A. Isoda, O. Moriya, M. L. Belladonna, H. Hayashi, Y. Iwakura, T. Yoshimoto, T. Akatsuka, and M. Matsui IL-23 Enhances Host Defense against Vaccinia Virus Infection Via a Mechanism Partly Involving IL-17 J. Immunol., September 15, 2007; 179(6): 3917 - 3925. [Abstract] [Full Text] [PDF]