title: Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages.
abstract: 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 beta-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.
authors.affiliation: Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaryo
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshimine
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tsuchihashi
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nagatake
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D056484:Jumonji Domain-Containing Histone Demethylases; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008997:Monobactams / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016209:Interleukin-8; D008997:Monobactams; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases