Disulfide bond formation between dimeric immunoglobulin A and the polymeric immunoglobulin receptor during hepatic transcytosis.
The polymeric immunoglobulin receptor on rat hepatocytes binds dimeric IgA on the sinusoidal surface and mediates its transport to the canaliculus, where the complex of dimeric IgA and secretory component, the cleaved extracellular domain of polymeric immunoglobulin receptor, is secreted into bile. This process is unique in that disulfide bonds are formed between dimeric IgA and polymeric immunoglobulin receptor during transcytosis, permanently preventing their dissociation. Here we present three lines of evidence that disulfide bonding between dimeric IgA and polymeric immunoglobulin receptor occurs predominantly in a late transcytotic compartment and that hepatic transcytosis can proceed in the absence of disulfide bond formation. First, throughout the course of transcytosis the percentage of intracellular dimeric IgA disulfide bonded to polymeric immunoglobulin receptor is less than half that in bile, suggesting that disulfide bond formation is a late event in transcytosis. Second, dimeric IgA that recycles from early endocytotic compartments into the circulation is mostly noncovalently bound to secretory component. Finally, the rate of transcytosis of dimeric IgA and its appearance in bile are not affected when disulfide bond formation with polymeric immunoglobulin receptor is inhibited by blocking of free thiol groups on dimeric IgA with iodoacetamide. These results are consistent with other findings in the literature and indicate that the main physiological role of disulfide bond formation between dimeric IgA and polymeric immunoglobulin receptor is not to facilitate transcytosis but, rather, to stabilize the dimeric IgA-secretory component complex after its release into external secretions such as bile and intestinal secretions.
Chintalacharuvu
K R
KR
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4943.
Tavill
A S
AS
Louis
L N
LN
Vaerman
J P
JP
Lamm
M E
ME
Kaetzel
C S
CS
D000818:Animals; D001646:Bile / Q000378:metabolism; D002451:Cell Compartmentation; D004220:Disulfides / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D007070:Immunoglobulin A / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism*; D012635:Secretory Component / Q000378:metabolism
D004220:Disulfides; D007070:Immunoglobulin A; D011108:Polymers; D011971:Receptors, Immunologic; D012635:Secretory Component