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.
Second Department of Internal Medicine, School of Medicine, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Yuji
Y
Ishimatsu
Jun-Ichi
J
Kadota
Tetsuji
T
Iwashita
Towako
T
Nagata
Hiroshi
H
Ishii
Chieko
C
Shikuwa
Hideyuki
H
Kaida
Hiroshi
H
Mukae
Shigeru
S
Kohno
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