Related Experiment Videos
Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1)
P D Williams1, D A Laska, T J Shetler
1Toxicology Division, Lilly Research Laboratories, Greenfield, Indiana 46140.
Abstract:
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.
Insights
Vancomycin can cause hypotension by triggering histamine release from mast cells. Rat mast cells are more sensitive to vancomycin-induced histamine release than RBL-1 cells, suggesting mast cells are a better model for studying this reaction.
Area of Science:
- Pharmacology
- Immunology
- Cell Biology
Background:
- Rapid intravenous vancomycin administration can cause hypotension.
- Histamine release from basophils and mast cells is implicated in vancomycin-induced hypotensive reactions.
- Antihistamine pretreatment can prevent these reactions.
Purpose of the Study:
- To investigate the direct effects of vancomycin on histamine release from rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells).
- To compare the sensitivity of mast cells and RBL-1 cells to vancomycin-induced histamine release.
- To evaluate the utility of mast cells versus RBL-1 cells as models for studying histamine release mechanisms.
Main Methods:
- Suspension cultures of rat peritoneal mast cells and RBL-1 cells were exposed to vancomycin at clinical concentrations (2.28 or 4.56 mg/ml) for 30-60 minutes.
- Histamine release was measured in the culture media.
- Compound 48/80 (CP 48/80) was used as a reference degranulating agent.
- The effects of cromolyn sodium on histamine release were assessed.
- Morphological evaluation of cell degranulation was performed.
Main Results:
- Vancomycin induced a time- and dose-dependent release of histamine from both mast cells and RBL-1 cells.
- Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells.
- Cromolyn sodium inhibited histamine release in mast cells but not in RBL-1 cells.
- Dose-related degranulation was observed in mast cells exposed to vancomycin or CP 48/80, but not reliably in RBL-1 cells.
Conclusions:
- Mast cells are more sensitive to vancomycin-induced histamine release than RBL-1 cells.
- Rat mast cells represent a more suitable model for evaluating agents that induce histamine release and for studying histamine release mechanisms compared to RBL-1 cells.