Modulation of the circulation and hepatic uptake of immune complexes by carbohydrate recognition systems

A. Rifai, D. S. Finbloom, D. B. Magilavy, P. H. Plotz

Research output: Contribution to journalArticle

Abstract

Stable model immune complexes of anti-DNP antibodies were prepared with multivalent affinity labeling antigens based on the polymer Ficoll derivatized with galactose or mannose. These oligomers were used in three series of experiments to examine the role of carbohydrate recognition systems in modulating the behavior of antigen-antibody complexes. The first series of experiments was designed to investigate the influence of particular monosaccharides on clearance and tissue uptake of model complexes. These experiments demonstrated that the addition of galactose or mannose to the Ficoll polymer backbone of the antigen accelerated clearance, particularly of small oligomers. Dimer complexes containing unglycosylated Ficoll were cleared slowly from circulation (t50 > 150 min) with less than 9% found in the liver at 30 min, whereas similar sized complexes containing galactose-derivatized Ficoll were cleared rapidly (t50 = 4 min) with 33% found in the liver. Small complexes containing mannose-derivatized Ficoll were removed at a moderate rate (t50 = 30 min) with an efficient liver uptake of 29% by 30 min. All heavy oligomers were removed rapidly (t50 ≤ 5 min) from the circulation, with a concomitant increase in liver uptake, 53 to 55% for Ficoll and galactose-Ficoll, and 75% for mannose-Ficoll complexes. In the second series of experiments, the blocking agents, asialoorosomucoid (ASOR), mannan, and heat-aggregated γ-globulin were used to examine the role of galactose-, mannose-, and Fc receptors, respectively, in the clearance and hepatic uptake of model complexes. ASOR specifically decreased the clearance and inhibited liver uptake of galactose-Ficoll complexes. Similarly, mannan specifically affected the clearance and liver uptake of small mannose-Ficoll complexes. Heavy oligomers of mannose-Ficoll were only slightly affected by either mannan or AHG. Analysis of the relative uptake of model immune complexes by hepatic nonparenchymal cells (NPC/PC) was performed in the last series of experiments. On a specific activity basis, galactose-Ficoll complexes were enriched in the parenchymal cell fraction (NPC/PC = 1.0), providing evidence for an active role of galactose receptors. Heavy oligomer with Ficoll (NPC/PC = 4) and mannose-Ficoll (NPC/PC = 10) were localized predominantly in the NPC fraction. The results indicate carbohydrate receptor recognizing an antigen in an immune complex may represent an alternative system to the antibody Fc receptors in modulating the clearance and subsequent fate of complexes.

Original languageEnglish (US)
Pages (from-to)2269-2275
Number of pages7
JournalJournal of Immunology
Volume128
Issue number5
StatePublished - 1982
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Rifai, A., Finbloom, D. S., Magilavy, D. B., & Plotz, P. H. (1982). Modulation of the circulation and hepatic uptake of immune complexes by carbohydrate recognition systems. Journal of Immunology, 128(5), 2269-2275.