Clearance kinetics and tissue distribution of aggregated human serum IgA in rats.
In the present study the clearance kinetics and tissue distribution of human polyclonal heat-aggregated serum IgA (AIgA) of different sizes in rats was studied after intravenous administration of 125I-AIgA. The 125I-AIgA of different sizes disappeared from the circulation in a biphasic manner with an initial rapid half-life (T1/2) and a second slower T1/2. The first T1/2 was related to the size of the 125I-AIgA: high molecular weight (MW) 125I-AIgA was cleared much faster than 125I-AIgA with a low MW. Relatively more degradation products were observed in blood when high MW 125I-AIgA were injected as compared to low MW 125I-AIgA. The AIgA were mainly taken up by the liver. Eight minutes after injection of high MW 125I-AIgA, 90% of the injected dose was found in the liver, whereas less than 2% was detected in the spleen. Very little activity was detectable in other organs, such as lungs, heart and kidneys. In the present study 1-3% of the injected 125I-AIgA were found in the bile. Analysis of this material revealed that low MW 125I-AIgA were transported more efficiently to the bile than high MW 125I-AIgA. To obtain more insight into the receptors involved in the clearance of 125I-AIgA, rats were pretreated with ovalbumin or asialofetuin. The clearance of 125I-AIgA of different sizes was inhibited when rats were pretreated with asialofetuin. Pretreatment with ovalbumin had no effect on the clearance rates of 125I-AIgA. These results suggest a role for carbohydrate receptors, which recognize glycoprotein-containing galactose terminal residues on Kupffer cells, in the clearance of 125I-AIgA.
Bogers
W M
WM
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Gorter
A
A
Stuurman
M E
ME
Van Es
L A
LA
Daha
M R
MR
D000818:Animals; D001212:Asialoglycoproteins; D001667:Binding, Competitive; D060748:Fetuins; D006801:Humans; D007070:Immunoglobulin A / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008970:Molecular Weight; D010047:Ovalbumin / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000008:administration & dosage; D014018:Tissue Distribution; D000509:alpha-Fetoproteins / Q000008:administration & dosage
D001212:Asialoglycoproteins; D060748:Fetuins; D007070:Immunoglobulin A; D046911:Macromolecular Substances; D000509:alpha-Fetoproteins; C017029:asialofetuin; D012965:Sodium Chloride; D010047:Ovalbumin