Journal article
The contribution of cell surface FcRn in monoclonal antibody serum uptake from the intestine in suckling rat pups
Frontiers in pharmacology, v 5, pp 225-225
07 Oct 2014
PMID: 25339905
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The neonatal Fc receptor (FcRn) in intestinal epithelium is the primary mechanism for transfer of maternal immunoglobulin G (lgG) from suckled milk to serum; but the factors contributing to the rapid uptake of IgG are poorly understood. These studies help to determine the contribution of cell surface FcRn in IgG uptake in 2-week-old rat pups by varying local pH and binding conditions. Variants of a human wild-type (WT) IgG monoclonal antibody (mAb WT) were assessed for binding affinity (K-D) to rat (r)FcRn at pH 6.0 and subsequent off-rate at pH 74 (1/s) by surface plasmon resonance. Selected mAbs were administered intra-intestinally in isoflurane-anesthetized 2-week rat pups. Full length mAb in serum was quantified by immunoassay, (r)FcRn mRNA expression by reverse transcription polymerase chain reaction, and mAb epithelial localization was visualized by immunohistochemistry. After duodenal administration, serum levels of mAb variants correlated with their rFcRn off-rate at pH 7.4, but not their affinity at pH 6.0. The greatest serum levels of IgG were measured when mAb was administered in the duodenum where rFcRn mRNA expression is greatest, and was increased further by duodenal administration in pH 6.0 buffer. More intense human IgG immunostaining was detected in epithelium than the same variant administered at higher pH. These data suggest an increased contribution for cell surface receptor. We conclude that, in the neonate duodenum, receptor off-rates are as important as affinities for FcRn mediated uptake, and cell surface binding of IgG to rFcRn plays contributes to IgG uptake alongside pinocytosis; both of which responsible for increased IgG uptake.
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Details
- Title
- The contribution of cell surface FcRn in monoclonal antibody serum uptake from the intestine in suckling rat pups
- Creators
- Philip R. Cooper - Johnson & JohnsonConnie M. Kliwinski - Johnson & JohnsonRobert A. Perkinson - Johnson & JohnsonEdwin Ragwan - Johnson & JohnsonJohn R. Mabus - Johnson & JohnsonGordon D. Powers - Johnson & JohnsonHaimanti Dorai - Johnson & JohnsonJill Giles-Komar - Johnson & Johnson Consumer Prod Inc, Janssen R&D, Biotechnol Ctr Excellence, Biol Res, Spring House, PA 19477 USAPamela J. Hornby - Johnson & Johnson
- Publication Details
- Frontiers in pharmacology, v 5, pp 225-225
- Publisher
- Frontiers Research Foundation
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000347147500001
- Scopus ID
- 2-s2.0-84909967019
- Other Identifier
- 991021931779104721
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- Web of Science research areas
- Pharmacology & Pharmacy