The adverse effects of smoking during pregnancy on fetal development are, in part, due to nicotine. These effects may be due to the actions of nicotine in fetal circulation or on placental functions. In pregnant rats, vaccination with a nicotine immunogen reduces the transfer of nicotine from the maternal to fetal circulation. However, extrapolation of these results to pregnant women might not be valid due to the well-recognized differences between human and rat placentas. In the current investigation, the effects of nicotine-specific antibodies on the transfer of nicotine from the maternal to fetal circuit of the dually perfused human placental lobule were determined. Two types of nicotine-specific antibodies were investigated; nicotine-specific mouse monoclonal antibody (Nic311, Kd for nicotine 60 nM) and IgG from rabbits vaccinated with a nicotine immunogen (Nic-IgG, Kd 1.6 nM). Transfer of the antibodies from maternal to fetal circuits was negligible. Both rabbit Nic-IgG and, to a lesser extent, mouse monoclonal Nic311 significantly reduced nicotine transfer from the maternal to fetal circuit as well as the retention of the drug by placental tissue. These effects were mediated by a substantial increase in the protein binding of nicotine and a reduction in the unbound nicotine concentration. Therefore, the data cited in this report suggest that the use of nicotine-specific antibodies might reduce fetal exposure to the drug, and that antibody affinity for nicotine is a key determinant of the extent of nicotine transfer.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Nov 25 2005|
Bibliographical noteFunding Information:
The authors would like to thank the physicians and nurses in Labor and Delivery in the Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas, for their assistance in obtaining placentas. They also greatly appreciate the assistance of the Chairman's Research Group and the Publication, Grant, & Media Support Office of the Department of Obstetrics & Gynecology. Nicotine-specfic rabbit IgG and the cell line used to produce Nic311 was kindly provided by Nabi Biopharmaceuticals. This work was supported by grants from NIDA to Paul Pentel (DA-015668 and P50 DA-013333) and to Mahmoud S. Ahmed (DA-13431).
- Human placenta
- Nicotine-specific antibodies
- Transplacental transfer