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Antimicrobial Agents and Chemotherapy, January 2003, p. 48-53, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.48-53.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Fourteen-Member Macrolides Promote the Phosphatidylserine Receptor-Dependent Phagocytosis of Apoptotic Neutrophils by Alveolar Macrophages

Takeshi Yamaryo,1 Kazunori Oishi,1* Hiroyuki Yoshimine,1 Yoshiko Tsuchihashi,1 Kouji Matsushima,2 and Tsuyoshi Nagatake1

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki,1 Department of Molecular Preventive Medicine, The University of Tokyo, Tokyo, Japan2

Received 6 May 2002/ Returned for modification 1 August 2002/ Accepted 2 October 2002

An inflammation of the airway of patients with diffuse panbronchiolitis (DPB), is characterized by dense neutrophil infiltration. Resolution of the inflammation can be achieved by the removal of apoptotic neutrophils by human alveolar macrophages (AM) without liberating neutrophil proteases in the airway. To understand clinical efficacy for the treatment of DPB by 14- or 15-member macrolides, their effects on the phagocytosis of apoptotic neutrophils by AM were examined. Treatment of AM with erythromycin (ERY) or clarithromycin at clinically achievable levels significantly increased the levels of phagocytosis of apoptotic neutrophils. A serum factor was not essential for the enhancement by these 14-member macrolides. Of the antibiotics tested, these effects were specific for the 14-member macrolides and a 15-member macrolide, azithromycin, but not for the 16-member macrolides, clindamycin or ß-lactam antibiotics. The enhanced phagocytosis of apoptotic neutrophils by ERY had no effect on the levels of interleukin-8 or tumor necrosis factor alpha production by lipopolysaccharide-stimulated AM after phagocytosis of the apoptotic neutrophils. The increased phagocytosis of apoptotic neutrophils by ERY was also found to be phosphatidylserine receptor-dependent for AM. These data indicate a novel anti-inflammatory action of 14-member and 15-member macrolides, and suggest that such antibiotics achieve clinical efficacy for patients with DPB, in part, through enhancing the nonphlogistic phagocytosis of apoptotic neutrophils by AM.

* Corresponding author. Mailing address: Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Phone: 81-95-849-7841. Fax: 81-95-849-7843. E-mail: oishi-k{at}net.nagasaki-u.ac.jp.

Antimicrobial Agents and Chemotherapy, January 2003, p. 48-53, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.48-53.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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