Talk:Immune System - Antibody Development: Difference between revisions

From Embryology
No edit summary
Line 16: Line 16:


==2012==
==2012==
===The Contribution of FcRn Binding to Intestinal Uptake of IgG in Suckling Rat Pups and Human FcRn-Transgenic Mice===
Am J Physiol Gastrointest Liver Physiol. 2012 Dec 6. [Epub ahead of print]
Kliwinski C, Cooper PR, Perkinson R, Mabus JR, Tam SH, Wilkinson TM, Giles-Komar J, Scallon B, Powers GD, Hornby PJ.
Source
1Janssen Pharmaceutical.
Abstract
Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn versus 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 isofluorane-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 (µg/mL) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-week-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, intra-intestinal hIgG1 WT administration resulted in dose-related and saturable uptake, whereas uptake of a low FcRn-binding affinity variant was non-saturable. 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 ~80% of serum hIgG levels, and IgG enters the circulation via the lymph and not the hepatic portal vein. The remaining uptake though the immature intestine is non-receptor 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.
PMID 23220220

Revision as of 11:42, 2 January 2013

About Discussion Pages  
Mark Hill.jpg
On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes:
  1. References - recent and historic that relates to the topic
  2. Additional topic information - currently prepared in draft format
  3. Links - to related webpages
  4. Topic page - an edit history as used on other Wiki sites
  5. Lecture/Practical - student feedback
  6. Student Projects - online project discussions.
Links: Pubmed Most Recent | Reference Tutorial | Journal Searches

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, March 29) Embryology Immune System - Antibody Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Immune_System_-_Antibody_Development

10 Most Recent

Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)

Fetal Antibodies

<pubmed limit=5>Fetal Antibodies</pubmed>

Antibody Development

<pubmed limit=5>Antibody Development</pubmed>

Neonatal Fc Receptor

<pubmed limit=5>Neonatal Fc Receptor</pubmed>


2013

2012

The Contribution of FcRn Binding to Intestinal Uptake of IgG in Suckling Rat Pups and Human FcRn-Transgenic Mice

Am J Physiol Gastrointest Liver Physiol. 2012 Dec 6. [Epub ahead of print]

Kliwinski C, Cooper PR, Perkinson R, Mabus JR, Tam SH, Wilkinson TM, Giles-Komar J, Scallon B, Powers GD, Hornby PJ. Source 1Janssen Pharmaceutical.

Abstract

Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn versus 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 isofluorane-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 (µg/mL) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-week-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, intra-intestinal hIgG1 WT administration resulted in dose-related and saturable uptake, whereas uptake of a low FcRn-binding affinity variant was non-saturable. 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 ~80% of serum hIgG levels, and IgG enters the circulation via the lymph and not the hepatic portal vein. The remaining uptake though the immature intestine is non-receptor 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.

PMID 23220220