Williams P D, Laska D A, Shetler T J, McGrath J P, White S L, Hoover D M
Toxicology Division, Lilly Research Laboratories, Greenfield, Indiana 46140.
Agents Actions. 1991 Mar;32(3-4):217-23. doi: 10.1007/BF01980877.
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.
快速静脉注射糖肽类抗生素万古霉素可能会引起低血压反应，通常可通过将万古霉素稀释后输注来预防。由于抗组胺药预处理可预防这种效应，因此循环细胞如嗜碱性粒细胞和组织肥大细胞释放组胺被认为与低血压反应有关。因此，研究了万古霉素对大鼠腹膜肥大细胞和大鼠白血病嗜碱性粒细胞（RBL-1细胞）组胺释放的直接影响。将肥大细胞或RBL-1细胞的悬浮培养物暴露于万古霉素中30 - 60分钟，浓度与临床输注浓度相当（2.28或4.56毫克/毫升）。万古霉素诱导两种细胞类型的组胺呈时间和剂量依赖性释放到培养基中。参比脱颗粒剂化合物48/80（CP 48/80）也被证明可诱导肥大细胞和RBL-1细胞释放组胺。肥大细胞对万古霉素和CP 48/80的敏感性明显高于RBL-1细胞，并且与RBL-1细胞不同，肥大细胞对色甘酸钠对组胺释放的抑制作用有反应。色甘酸钠不抑制RBL-1细胞或肥大细胞中万古霉素诱导的组胺释放。形态学上观察到，暴露于万古霉素或CP 48/80的肥大细胞呈现出剂量相关的脱颗粒现象。另一方面，通过定性评估，无法可靠地区分万古霉素或CP 48/80对RBL-1细胞的处理相关脱颗粒效应与对照。基于这些发现得出结论，与RBL-1细胞相比，肥大细胞可能是评估研究药物释放组胺潜力和研究组胺释放机制更有用的模型。
