Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1).
Rapid intravenous administration of the glycopeptide antibiotic, vancomycin, may cause a hypotensive reaction which can usually be prevented by infusing vancomycin in dilute solutions. The release of histamine from circulating cells such as basophils and tissue mast cells has been implicated in hypotensive reactions since the effects can be prevented by antihistamine pretreatment. The direct effects of vancomycin on histamine release were therefore investigated in rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells). Suspension cultures of mast cells or RBL-1 cells were exposed to vancomycin for 30-60 minutes at concentrations comparable to those infused clinically (2.28 or 4.56 mg/ml). Vancomycin induced a time- and dose-dependent release of histamine into the culture media from both cell types. The reference degranulating agent, Compound 48/80 (CP 48/80), was also shown to induce histamine release from mast cells and RBL-1 cells. Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells and, unlike RBL-1 cells, were responsive to the inhibitory effects of cromolyn sodium on histamine release. Cromolyn sodium did not inhibit vancomycin-induced histamine release in RBL-1 or mast cells. Morphologically, mast cells exposed to either vancomycin or CP 48/80 exhibited dose-related degranulation. On the other hand, treatment-related degranulation effects of either vancomycin or CP 48/80 on RBL-1 cells could not be reliably distinguished from controls by qualitative evaluation. Based upon these findings it is concluded that mast cells may represent a more useful model to evaluate the potential of investigational agents to release histamine and to study mechanisms of histamine release than RBL-1 cells.
Williams
P D
PD
Toxicology Division, Lilly Research Laboratories, Greenfield, Indiana 46140.
Laska
D A
DA
Shetler
T J
TJ
McGrath
J P
JP
White
S L
SL
Hoover
D M
DM
D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004205:Cromolyn Sodium / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010529:Peritoneal Cavity / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D014640:Vancomycin / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003189:p-Methoxy-N-methylphenethylamine; D014640:Vancomycin; D004205:Cromolyn Sodium