Hapten inhibition of passive antidextran dextran anaphylaxis in guinea pigs. Role of molecular size in anaphylactogenicity and precipitability of dextran fractions.

Abstract

High titred antidextran antisera have been raised in rabbits by prolonged immunization with soluble conjugates between isomaltose oligosaccharides or dextran m<sub>w</sub> 4,400 and bovine serum albumin in complete Freund’s adjuvant. Guinea pigs sensitized with such antisera exhibited anaphylactic shock on i.v. challenge with fractions of hydrolyzed B512 dextran. The severity of anaphylaxis depended on the amount of sensitizing antibody and the dose and molecular size of the challenging dextran fraction. In maximally sensitized animals, fractions of m<sub>w</sub> 3,600 or larger were anaphylactogenic and smaller molecular size fractions were nonanaphylactogenic. In submaximally sensitized animals, dextran fractions of m<sub>w</sub> 10,500 or less were foundnonanaphylactogenic. In addition, nonanaphylactogenic dextran fractions produced desensitization, i.e. protection from anaphylaxis due to subsequent or simultaneous injection of more high molecular and anaphylactogenic dextran fractions. When the molar ratio in a mixture of nonanaphylactogenic/anaphylactogenic fractions was about 7.6, protection was complete with reduction of mortality from 100 to 0%. A molar ratio of 1.9, corresponding to a 13-percent by weight admixture of nonanaphylactogenic dextran, still significantly reduced mortality from 100 to 50%. From the ability to form precipitates with antidextrans and to elicit anaphylaxis in sensitized guinea pigs, and from the absence of these properties, the approximate molecular size range of bivalent and monovalent dextran B512 fractions was found to correspond to m<sub>w</sub> 3,600 and m<sub>w</sub> 1,430, respectively. The practical applicability of hapten inhibition is discussed.