STUDIES ON THE MECHANISMS OF HYPERSENSITIVITY PHENOMENA

TLDR

Human leukocytes from ragweed‑sensitive donors release histamine when exposed to a purified pollen protein antigen, and optimal reactivity requires physiological pH, ionic strength, temperature, calcium, and magnesium. The study measured cellular sensitivity in approximately 200 ragweed‑sensitive donors and examined the kinetics of antigen‑induced histamine release. Histamine release was investigated using washed leukocytes in a defined serum‑free medium, showing that chelating divalent cations or lowering temperature halts the reaction, and that desensitization can be induced by exposing cells to antigen in a cation‑deficient environment followed by restoration of optimal conditions. The release rate depends on antigen concentration but always shows a lag phase; desensitization procedures reduce reactivity, and the data support that histamine release is an active, enzymatically mediated multistep response to antigen.

Abstract

Human leukocytes, isolated from the blood of ragweed-sensitive donors, release histamine upon reaction with a purified protein antigen derived from this pollen. The release process has been studied with washed cells suspended in a defined, serum-free medium. Physiologic levels of pH, ionic strength, and temperature, as well as both calcium and magnesium, are required for optimal cellular reactivity. The level of cellular sensitivity of approximately 200 ragweed-sensitive donors has been ascertained, and the kinetics of the release process studied. The rate of histamine release is a function of antigen concentration, but even with a large excess of this reagent it is impossible to abolish a lag phase. Chelation of the divalent cations or a decrease in the reaction temperature may be utilized to stop the reaction. These measures are effective both before and after the initiation of histamine release. Diminished cellular reactivity (desensitization) has been achieved by several procedures. These have in common the addition of antigen to cells in an environment deficient in but a single respect, followed by a restoration of optimal conditions. The significance of these data has been discussed and it has been proposed that immunologically induced histamine release is an active, enzymatically mediated process which occurs as a multistep response of viable cells to a specific antigenic stimulus.