Journal article
Contribution of FcRn binding to intestinal uptake of IgG in suckling rat pups and human FcRn-transgenic mice
American journal of physiology: Gastrointestinal and liver physiology, v 304(3), pp G262-G270
01 Feb 2013
PMID: 23220220
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Kliwinski C, Cooper PR, Perkinson R, Mabus JR, Tam SH, Giles-Komar TM, Scallon B, Powers GD, Hornby PJ. Contribution of FcRn binding to intestinal uptake of IgG in suckling rat pups and human FcRn-transgenic mice. Am J Physiol Gastrointest Liver Physiol 304: G262-G270, 2013. First published December 6, 2012; doi:10.1152/ajpgi.00340.2012.-Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn vs. FcRn-independent uptake to serum IgG levels had not been determined in either rat pups or human (h) FcRn-expressing mice (Tg276 and Tg32). In isoflurane-anesthetized rodents, serum levels were determined after regional intestinal delivery of human monoclonal antibodies (hIgG) with either wild-type (WT) Fc sequences or variants engineered for different FcRn binding affinities. Detection of full-length hIgG was by immunoassay; intestinal hFcRn and hIgG localization was by immunocytochemistry. High (mu g/ml) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-wk-old rats. Human FcRn was visualized in epithelial cells of Tg276 mice, but low serum hIgG levels (<10 ng/ml) were obtained. In rat pups, intraintestinal hIgG1 WT administration resulted in dose-related and saturable uptake, whereas uptake of a low FcRn-binding affinity variant was nonsaturable. There were no differences in hIgG levels from systemic and hepatic portal vein serum samples, and intense hIgG immunostaining was noted in villi enterocytes and within lymphatic lacteal-like vessels. This study demonstrated that FcRn-mediated uptake in rat pups accounted for similar to 80% of serum hIgG levels and that IgG enters the circulation via the lymph and not the hepatic portal vein. The remaining uptake though the immature intestine is nonreceptor mediated. Intestinal epithelial cell hFcRn expression occurred in Tg276 mice, but receptor-mediated transport of IgG was not observed. The suckling rat pup intestine is a mechanistic model of FcRn-IgG-mediated transcytosis.
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Details
- Title
- Contribution of FcRn binding to intestinal uptake of IgG in suckling rat pups and human FcRn-transgenic mice
- Creators
- C. Kliwinski - Johnson & JohnsonP. R. Cooper - Johnson & JohnsonR. Perkinson - Johnson & JohnsonJ. R. Mabus - Johnson & JohnsonS. H. Tam - Johnson & JohnsonT. M. Wilkinson - Johnson & JohnsonJ. Giles-Komar - Johnson & JohnsonB. Scallon - Johnson & JohnsonG. D. Powers - Johnson & JohnsonP. J. Hornby - Johnson & Johnson
- Publication Details
- American journal of physiology: Gastrointestinal and liver physiology, v 304(3), pp G262-G270
- Publisher
- Amer Physiological Soc
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000314644600005
- Scopus ID
- 2-s2.0-84873362213
- Other Identifier
- 991021931909104721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Gastroenterology & Hepatology
- Physiology