Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro.
We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease. To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood. Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 microg/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not. Our results suggest that macrolides induce apoptosis of lymphocytes through Fas-Fas ligand pathway and could potentially reduce the number of lymphocytes in the lungs of patients with chronic lower respiratory tract disease.
Ishimatsu
Yuji
Y
Second Department of Internal Medicine, School of Medicine, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Kadota
Jun-Ichi
J
Iwashita
Tetsuji
T
Nagata
Towako
T
Ishii
Hiroshi
H
Shikuwa
Chieko
C
Kaida
Hideyuki
H
Mukae
Hiroshi
H
Kohno
Shigeru
S
D017304:Annexin A5 / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis; D017963:Azithromycin / Q000494:pharmacology; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D015570:Josamycin / Q000009:adverse effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D018942:Macrolides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D013997:Time Factors; D019014:fas Receptor
D017304:Annexin A5; D000900:Anti-Bacterial Agents; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018942:Macrolides; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D017963:Azithromycin; D017291:Clarithromycin; D015570:Josamycin