Antigen specific histamine release

Protein Fv binds specifically to the VH domain of immunoglobulins [22], Consequently, this endogenous protein is similar to multivalent antigens or to divalent anti-IgE antibodies. To evaluate the mechanism whereby this protein activates basophils, we incubated protein Fv with human monoclonal IgM from diverse VH families [19,29], Preincubation of basophils with three preparations of human monoclonal IgM VH3+ concentration-dependently inhibited the histamine-releasing activity of protein Fv. In contrast, a monoclonal IgM that has a Vh6 domain had no such effect. These results are compatible with the hypothesis that protein Fv binds to IgE VH3 + bound to FceRI+ cells. 

Pyrilamine competitively antagonizes histamine at the H,-receptor site but does not bind with histamine to inactivate it. Terfenadine and astemizole, the most specific Hj antagonists available, bind preferentially to peripheral rather than central Hj receptors. Antihistamines do not block histamine release, antibody production, or antigen-antibody interactions. They antagonize in varying degrees most of the pharmacological effects of histamine. 

Anaphylaxis occurs when a patient with antigen-specific immunoglobulin E (IgE) bound to the surface of mast cells and basophils is exposed to the antigen, triggering the release of histamine and various other vasoactive compounds. 

The same pattern of specificity was found by Goth et al. (1971) on histamine release from isolated mast-cells during antigen-antibody interaction by Pepeu et al. (1976) on the Ach-release from rat cortex by Bruni et al. (1976b) on the increase of brain glucose. Lloyd Kaufman (1974) found that PS specifically stimulates tyrosine hydroxylase activity in bovine caudate nucleus, while Raese et al., (1976) found that PS stimulates the tyrosine hydroxylase also in rat striatum. 

A few examples of atopic states in which correlations have been found between levels of specific IgE antibodies and the presence of clinical symptoms are aUei gy to horse dandruff or timothy pollen (231), cod extract, bird poUen, house dust (232), animal danders, and various pollens (233). Zeiss et al. (234) observed a highly significant correlation between levels of IgE antibody specific for ragweed antigen E and the sensitivity of the patients leukocytes to the antigen, as evidenced by histamine release. 

The current descriptions of sensitivity and maximal response are best applied to secretion of histamine. However, a more complete understanding will require further information about the same parameters in the context of lipid and cytokine release. Both of these mediators are critical determinants of the allergic inflammatory response, so that understanding the extent to which new therapeutics need to suppress basophil and mast cell responsiveness will be dependent on new information regarding the relative roles of each of the secreted mediators. Recent studies have indicated that basophil sensitivity is very similar when viewed from the secretion of each of three classes of mediators. This means that if cell surface antigen-specific IgE is present at a density sufficient to initiate only 50% of the maximum histamine release, approximately 50% of the maximal secretion of IL-4 and LTC4 will also be obtained. It remains to be determined whether the equivalent suppression of secretion for each of the three classes of mediators will lead to equivalent reductions for the functional endpoints of the three different mediator classes. 

Figure 4 Relationship between the ratio of pretreatment D. farinae-specific IgE to total IgE and the change in basophil response following treatment with rhuMAb-E25. The ratio of specific to total IgE is not absolute, the assay for D. /annae-specific IgE has not been calibrated against standard IgE preparations. The output measure from this assay is in KIU per mL of serum. The basophil response is expressed as the ratio of posttreatment to pretreatment histamine release basophils were from whole blood by PercoU single step gradients and challenged in vitro with an optimal concentration of D. farinae antigen.

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