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Intestinal Uptake of Macromolecules

II. Effect of Parenteral Immunization¹

From the Department of Medicine, Harvard Medical School and the Gastrointestinal, Arthritis and Clinical Immunology Units of the Medical Services, Massachusetts General Hospital, Boston, Massachusetts 02114

Abstract

Rats were parenterally immunized with bovine serum albumin (BSA) and horseradish peroxidase (HRP) emulsified in complete Freund's adjuvant; absorption of these antigens was tested in vitro by means of the everted gut sac technique. A significant and specific decrease in uptake of BSA was noted in rats injected five times with BSA, but not in rats injected only twice. Absorption of ¹²⁵I-HRP and HRP, measured enzymatically, was also significantly inhibited in rats immunized five times with HRP. The binding of ¹²⁵I-BSA to intestinal secretions, mucosal extracts and serum from rats showing interference with BSA absorption (multiple injections) was 2- to 10-fold greater than that of comparable preparations from rats which did not show interference (injected twice). Antigen-binding to IgG_a, IgG1, and IgM antibodies was demonstrated by radioimmunoelectrophoresis in the serum of rats with multiple injections of BSA; in addition, binding to IgG_a and IgG1 antibodies was demonstrated with mucosal extracts. Although antigen uptake was inhibited in rats immunized parenterally with BSA and HRP, the number of gut sacs showing an inhibited response and the extent of the response were less than that previously observed with gut sacs obtained from rats immunized orally with the same antigens. Binding activity of ¹²⁵I-BSA in mucosal extracts from this latter group of rats was the same as in rats parenterally immunized but only IgG1 antibodies were noted in mucosal extracts. It was suggested that the more consistent inhibition of antigen uptake in orally immunized vs parenterally immunized rats may be related to the type or pattern of local antibody distribution.

Footnotes

¹ This work was supported in part by grants from the National Institutes of Health (AM-03014, AM-5067, AM-3564, TIAM-05146, AI-10129); the United States Army Medical Research and Development Command (Contract DADA-17-70-C-0113) and Massachusetts Chapter, Arthritis Foundation.

² Dr. Walker is a recipient of a Research Fellowship from the Medical Foundation, Inc., Boston, Massachusetts.

Address reprint requests to: Dr. W. A. Walker, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114.

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