Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions

S. S. Rich, C. S. David

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Abstract

Proteolytic cleavage and activation of isolated, single chain, zymogen Hageman factor was observed in the presence of kaolin alone. The rate of cleavage of kaolin-bound Hageman factor was enhanced 50-fold by the presence of prekallikrein and high molecular weight kininogen. The 2-chain 82,000 dalton form of activated Hageman factor [α-HF(a)] also cleaved kaolin-bound single-chain Hageman factor in a dose-dependent manner, yielding fragments of 28,000 and 50,000 daltons under reducing conditions. Cleavage of kaolin-bound single-chain Hageman factor was not inhibited by preincubation with diisopropylfluorophosphate (12 mM) for 10 min, but long-term incubation of Hageman factor with diisopropylfluorophosphate (up to 48 hr) resulted in inhibition of cleavage of kaolin-bound Hageman factor to an extent proportional to the inhibition of procoagulant Hageman factor activity. Hageman factor cleavage was maximal when the kaolin concentration was ~ 10-fold greater than the Hageman factor concentration (wt:wt), and was partially inhibited by high molecular weight kininogen. Kaolin-bound Hageman factor cleaved clotting factor XI in an amount which correlated with the extent of cleavage of the Hageman factor. The findings are compatible with the concept that single-chain Hageman factor and α-HF(a) are both capable of cleaving and activating kaolin-bound Hageman factor and that a close molecular association of kaolin-bound Hageman factor molecules is required for this reaction.

Original languageEnglish (US)
Pages (from-to)1108-1121
Number of pages14
JournalJournal of Experimental Medicine
Volume150
Issue number5
StatePublished - 1979

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ASJC Scopus subject areas

  • Immunology

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