High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: cation-exchange chromatography coupled with post-column derivatization fluorometry

Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines-macrophage inflammatory protein 1alpha/monocyte chemoattractant protein 1-and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s. c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores "normal" inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials.

https://www.pnas.org/content/pnas/95/15/8841.full.pdf

Mast cells mediate acute inflammatory responses to implanted biomaterials

Platelet-activating factor is a novel phospholipid that has been implicated as an important mediator of acute allergic reactions. The intravenous administration of acetyl glyceryl ether phosphorylcholine, a pure, synthetic platelet-activating factor, causes electrocardiographic changes in the rabbit similar to those which are characteristic manifestations of systemic anaphylaxis. To determine whether platelet-activating factor contributes to anaphylactic cardiac dysfunction, we measured platelet-activating factor release from the sensitized guinea pig heart challenged in vitro with specific antigen and compared the resulting cardiac dysfunction with that induced by the injection of acetyl glyceryl ether phosphorylcholine into nonsensitized hearts. The results of these studies document that, during anaphylaxis in the isolated guinea pig heart, a platelet-activating factor is released into the coronary effluent that has physicochemical and functional properties similar to those of acetyl glyceryl ether phosphorylcholine. The intracardiac administration of acetyl glyceryl ether phosphorylcholine (10(-14) to 3 X 10(-9) mol) induced dose-related decreases in left ventricular contractile force (-5 to -85%) and coronary flow (-5 to -85%), as well as impaired atrioventricular conduction. The negative inotropic effect of acetyl glyceryl ether phosphorylcholine also was present in hearts perfused at constant flow. Although, in these hearts, acetyl glyceryl ether phosphorylcholine increased coronary resistance, which may have caused regional shunting and ischemia, it is unlikely that the negative inotropic effect of acetyl glyceryl ether phosphorylcholine was secondary to changes in coronary flow, since acetyl glyceryl ether phosphorylcholine also caused a dose-dependent negative inotropic effect in the electrically paced, noncoronary-perfused left atrium and right ventricular papillary muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl glyceryl ether phosphorylcholine (AGEPC). A putative mediator of cardiac anaphylaxis in the guinea pig.

Modification of the cardiac rhythm by histamine has been appreciated almost since the compound's isolation from ergot by Barger and Dale in 1910. The major arrhythmogenic actions of histamine are an Hi-receptor-mediated slowing of atriovenrricular (AV) conduction and H2-receptor-mediated increases in sinus rate and ventricular automaticity. These actions were elucidated by observing the salutary effects of histamine antagonists on the arrhythmias of anaphylaxis, and by administering exogenous histamine to various cardiac preparations in the presence and absence of histamine antagonists. The ability to record transmembrane action potenrial(s) (TAP) from single cells has permitted the study of electrophysiological mechanisms underlying histamine-induced arrhythmias.

Histamine and cardiac arrhythmias.

In an attempt to facilitate the diagnosis of mastocytosis, we measured the urinary excretion of histamine and two of its main metabolites (Nτ-methylhistamine and Nτ-methylimidazoleacetic acid) in eight adults with this disorder. All patients had above-normal values for the metabolites of histamine, whereas only three had above-normal values for histamine. In both 24-hour and randomly voided urine specimens, the determination of histamine metabolites is more specific and sensitive for the diagnosis of mastocytosis than the determination of histamine itself. (N Engl J Med 1983; 309:1603–5.)

Improved diagnosis of mastocytosis by measurement of urinary histamine metabolites.

Topics related to the measurement of histamine in human plasma and other body fluids are reviewed. These include (1) an overview of the data obtained by the biological, fluorometric and radioenzymatic assays over the past 45 years; (2) the various modifications of the radioenzymatic isotopic assay of histamine and the development of a single extraction step assay; (3) a compilation of values obtained in our laboratory by the radioenzymatic assay of histamine levels in various body fluids in disease states associated with abnormal histamine production or release; and (4) factors that affect histamine levels in plasma and some experimental considerations for monitoring changes in free histamine levels. The last topic includes a discussion of the halflife of histamine in the circulation, its clearance across various vascular beds, and the fact that capillary endothelial cells are one site of inactivation of circulating histamine.

M A Beaven

Papers

The demonstration of histamine release in clinical conditions: a review of past and present assay procedures.