Details

Autor(en) / Beteiligte

• Hornby, Pamela Janet
• Cooper, Philip R
• Kliwinski, Connie
• Ragwan, Edwin
• Mabus, John R
• Harman, Benjamin
• Dorai, Haimanti
• Giles‐Komar, Jill

Titel

FcRn Expression and Antibody Transcytosis in Adult Human and Non‐Human Primate Intestine

Ist Teil von

• The FASEB journal, 2013-04, Vol.27 (S1)

Erscheinungsjahr

2013

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Abstract only The neonatal Fc receptor (FcRn) expressed in duodenal epithelial cells transports immunoglobulin G (IgG) in lactated milk into the newborn lamina propria, but its role in IgG transcytosis in adults is unknown. Therefore, we assessed the following: FcRn expression on human intestinal epithelial (hInEp) cells (flow cytometry and binding); transcytosis of IgG in human intestinal segments mounted in Ussing‐type flux chambers by ELISA; FcRn (mRNA and protein) expression in adjacent mucosa; serum IgG uptake after intestinal administration in isofluorane‐anesthetized cynomolgus monkeys. Surface expression and FcRn‐dependent binding of IgG was shown in caco‐2 and hInEp cells. Human intestinal villi enterocytes were FcRn‐immunostained; unexpectedly, FcRn +ve staining in crypt cells was colocalized with GLP‐1, GLP‐2 and CCK in enteroendocrine cells. Higher mucosal FcRn mRNA and protein expression was associated with greater luminal to serosal flux of mAb in human intestinal segments. In cynomolgus monkeys, serum levels of full‐length mAb (0.3% dose) were detected after direct infusion of mAb into ileum/proximal colon (2 mg/kg; n=3), but not after oral gavage. FcRn intestinal expression contributes to fractional uptake of mAb delivered intestinally; however epithelial cell mAb transcytosis is unlikely to be mediated solely by surface FcRn. The function of FcRn in enteroendocrine cells is unknown.