Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions.

This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A). The release process is initiated by the interaction of antigen on anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the relase of histamine and other mediators of the immediate hypersensitivity reaction. The dose-response relationships and kinetics of histamine and BK-A release from antigen-challenged peripheral leukocytes are similar.

Anaphylactic release of a basophil kallikrein-like activity. I. Purification and characterization.

These studies describe the IgE-mediated relase of a basophil kallikrein-like enzyme that is an arginine esterase and is inhibited by plasma, diisopropylphosphofluoridate, and Trasylol. The substrate specificity for the synthetic amino acid ester substrates p-toluenesulfonyl-L-arginien methyl ester, benzoyl-arginine methyl ester, and acetyl-tyrosine methyl ester is similar for the basophil enzyme and plasma kallikrein. The interaction of arginine esterase-active fractions from ion-exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen, generates immunoreactive kinin.

Spontaneous histamine secretion from leukocytes in the presence of strontium.

Basophil leukocytes from human blood secrete histamine in the absence of a membrane stimulus when incubated in a medium containing Sr++, 1 to 10 mM. Spontaneous histamine secretion in the presence of Sr++ is inhibited by La+++, 1 to 1000 nM and 2 deoxy-D-glucose, 30 to 300 microM. Spontaneous secretion in the presence of Sr++ increases with increasing pH in the range 6.

The action of strontium on basophil leukocytes and its use to probe the relationship between immunologic stimulus and secretory response.

Strontium will substitute for calcium in the activation of histamine secretion from human basophil leukocytes stimulated by an immunologic reaction or by the ionophore A23187. Strontium is required in 10-fold higher concentration (1 to 10 mM) to activate histamine release compared with calcium (0.1 to 1.

Effect of solvent on the histamine-releasing, enzyme-releasing, and mitogenic properties of the calcium ionophore A23187.

The potency of the calcium ionophore A23187 in inducing three activities of human leukocytes (histamine secretion from basophils, enzyme secretion from PMNs, and proliferation of lymphocytes) was markedly dependent on the solvent (DMSO versus ethanol versus aqueous buffer) used for its initial sonication. While 0.1 micrograms/ml of DMSO- and ethanol-solubilized A23187 induced maximal histamine release from basophils and histaminase release from PMNs, concentrations of aqueous buffer-sonicated ionophore of greater than or equal to 1 microgram/ml were required for an equivalent response.

Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro.

Since extracellular adenosine is a physiologically important regulator of adenylate cyclase and cell function in various mammalian tissues, we have examined the effect of adenosine on histamine release from human basophils. Adenosine inhibited IgE-mediated histamine release by its ability to increase leukocyte cyclic AMP levels; the same concentrations of adenosine which inhibited histamine release increased the cyclic AMP level of mixed leukocytes. Inhibition of histamine release was also observed with an adenosine deaminase (ADA) inhibitor [erythro-9-(2-hydroxy-3-nonyl)-adenine: EHNA] in the presence of autologous serum.

In vitro studies of antigen-induced bronchospasm: effect of antihistamine and SRS-A antagonist on response of sensitized guinea pig and human airways to antigen.

Exposure of sensitized guinea pig tracheal rings or human bronchial strips to specific antigen in vitro resulted in a rapidly developing, prolonged contraction that was resistant to washing. Treatment of the tissue with diphenhydramine, a histamine H1 antagonist, before antigen delayed the onset and decreased the amplitude of the initial phase of the contraction but did not reduce the duration. Diphenhydramine treatment after development of the contraction did not relax the airway tissue.

Basophil kallikrein of anaphylaxis (BK-A)--purification and characterization.

These studies describe the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) that has arginine esterase activity and is inhibited by plasma, DFP, and Trasylol. The interaction of BK-A active fractions from ion exchange (DEAE-Sephacel) and gel filtration (Sepharose 6B) chromatography, with human plasma kininogen generates immunoreactive kinin. The BK-A and kinin-generating activities co-chromatograph on DEAE-Sephacel and Sepharose 6B columns, and the quantity of kinin generated is, in general, proportional to the BK-A activity of the column fractions, suggesting that these two activities are subserved by the same protease.

Activation of human Hageman factor by a leukocytic protease.

We earlier reported the IgE-mediated release of a basophil kallikrein of anaphylaxis (BK-A) which, like plasma kallikrein, is an arginine esterase and cleaves human plasma kininogen generating immunoreactive kinin. We herein report that, like plasma kallikrein, preparations rich in this basophil protease also activate human Hageman Factor by proteolytic cleavage of the zymogen molecule into light and heavy chains. These fragments of 28,000 and 52,000 daltons are similar in size to those produced during activation of Hageman Factor by plasma kallikrein.

Passive sensitization of human basophils: evidence for heterogeneity in the IgE molecule.

Possible functional heterogeneity of human IgE antibody was studied by passively sensitizing human basophils for antigen-induced histamine release. Six sera of known IgE anti-ragweed antigen E and total IgE content were diluted to contain 10 ng of antibody but differed with respect to the ratio of specific/total IgE. The relative ability of the sera to passively sensitize generally reflected the specific/total IgE ratio but one serum was 2.

Allergy to insect stings. IV. Diagnosis by radioallergosorbent test (R.A.S.T.).

Radioallergosorbent tests (RAST(s)) have been developed and assessed for the diagnosis of insect hypersensitivity by using a purified allergen from honeybee venom, phospholipase A, and crude yellow jacket venom. Sera from 193 patients positive both by history and skin test to one of these insects were compared with various groups of control sera. Eighty percent of sera from skin test-positive patients were RAST positive; positive RAST were found in 16% of sera tested from skin test-negative patients.

Characterization of a specific adenosine receptor on human lymphocytes.

We have examined the mechanism of action of adenosine, a naturally occurring nucleoside that has profound effects on lymphocyte function. Adenosine (0.01 micrometer to 10 micrometer) increased lymphocytes cAMP levels in a dose-dependent fashion with a maximal (10 micrometer) increase of about 4-fold, whereas adenine, guanosine, and inosine had no effect on lymphocyte cAMP levels at concentrations of 100 micrometer.

Protein allergens of white-faced hornet, yellow hornet, and yellow jacket venoms.

White-faced hornet, yellow hornet, and yellow jacket venoms have very similar protein compositions; each contains mainly three basic proteins. Two of these proteins have hyaluronidase and phospholipase activities and the third one, designated as antigen 5, is of as yet unidentified biochemical function. These three proteins have molecular weights of about 45 000, 35 000, and 25 000, respectively.

A controlled trial of immunotherapy in insect hypersensitivity.

Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively.

IgE receptors on human basophils. Relationship to serum IgE concentration.

As reported previously, and confirmed here in 26 donors, the serum IgE level (2.6-5,500 ng/ml) correlates well (rs = 0.95, P less than 0.

The role of basophils in inflammatory reactions.

This review demonstrates that basophils reflect skin and lung mast cell reactivity and show characteristic changes in mediator release associated with clinical disease. Although the numbers of IgE molecules and IgE receptors on basophils have been enumerated, these have, in most instances, little influence on the release of histamine after challenge. There is, rather, a parameter of "releasability" that may be a major variable in allergic disease states.

Histamine release due to bivalent penicilloyl haptens: control by the basophil plasma membrane.

We describe the characteristics of in vitro histamine release from human basophils passively sensitized with serum from a penicillin-allergic individual. The histamine release is induced by a synthetic bivalent hapten, bis benzylpenicilloyl 1,6 diaminohexane (BPO)2. We present data on the effect of a monovalent hapten, benzylpenicilloyl formyl-L-lysine (BPO)1, on the histamine release.