Analysis of compound 48/80-induced skin histamine release and leukotriene production in chronic urticaria.

Profiles of histamine release by nonlesional skin mast cells from patients with chronic urticaria (CU) and normal control (NC) subjects were compared on stimulation with a wide range of concentrations of compound 48/80 (0.15 to 4.8 mg/ml). One previous observation demonstrating spontaneous and 48/80-induced release of histamine greater in patients with CU than in NC subjects was confirmed with a concentration of 48/80 believed to produce mast cell activation in most subjects (2.4 mg/ml). In fact, higher concentrations of histamine were released by patients with CU than by NC subjects on stimulation with 48/80 at concentration greater than 0.6 mg/ml. With 0.6 mg/ml of 48/80, the profiles of histamine release were comparable in the two groups, and for concentration less than 0.6 mg/ml, the profiles of release were completely different, being higher in NC subjects than in the group with CU. The peak histamine response was higher in the group of NC subjects (6500 pg/ml) than in the group with CU (5100 pg/ml), and the concentration of 48/80 needed to trigger maximum release was lower in the NC subjects than in the subjects with CU (0.15 versus 0.6 mg/ml). The production of leukotriene B4 and leukotriene C4 was also compared in these two groups after stimulation with 2.4 mg/ml of compound 48/80. No significant amount of leukotriene B4 was found in the collection chambers, but small amounts of leukotriene C4 were measured into skin chamber fluids during a period of 4 hours. No significant difference could then be observed between the two groups.

Basophil histamine release in insect venom allergy.

The aim of the present study was to investigate venom-related and venom-non-related immunological reactions in patients stung by bee or wasp. Sixteen consecutive patients (7 with local and 9 with systemic reactions) were tested with skin tests, RAST and basophil histamine release (BHR) test immediately after the insect sting and 2, 4, and 16 weeks later. No test was useful immediately after the insect sting, the "anergic period". In agreement with earlier findings, the SPT was the only allergy test that showed statistically significant differences between patients with local and systemic reactions, although a great overlap was found. Release of histamine from basophils after incubation with anti-IgE also showed statistically significant differences between local and systemic reactions. Further studies are needed, especially measurement of BHR after incubation with anti-IgE before insect stings.

Influenza A virus potentiates basophil histamine release caused by endotoxin-induced complement activation. Examination of normal individuals and patients with intrinsic asthma.

Histamine release from human basophil leukocytes was triggered by complement activation by means of endotoxins isolated from E. coli and Salmonella bacteria. Influenza A virus was found to enhance the mediator release, and the effect was caused by synergism, since virus itself did not release histamine. The potentiating effect was similar in cells from normal individuals and from patients with intrinsic asthma. The involvement of viral neuraminidase was examined by a potent neuraminidase inhibitor and this inhibitor completely abolished the potentiating effect by virus. A purified neuraminidase preparation obtained from Vibrio cholerae caused a similar potentiating effect in mediator release and the effect was abolished by the neuraminidase inhibitor. These findings indicate that viral neuraminidase is responsible for the potentiating effect of virus on the histamine release. This effect might play a role in septic conditions and possibly contribute to asthmatic attacks by infections.

Early cellular events in pulmonary fibrosis.

In this review we have surveyed recent investigations of early cellular events in pulmonary fibrosis both in animal models and in human diseases. Analysis of the interactions of the numerous cell types in the lung following injury is an almost overwhelmingly complex enterprise. In the animal models experimental design has a profound effect on results, making it difficult to compare studies when species, fibrogenic agent, dose, route of exposure, schedule of administration, time course, and analytical methods may not be equivalent. In human diseases we are rarely able to obtain data at precisely the same time point in the course of the disease even among patients in the same study, and possible confounding variables present are legion. Transcending these difficulties for the moment, can we draw any conclusions from our current knowledge of early cellular interactions in pulmonary fibrosis? What is striking is not that there are so many agents that can potentially induce pulmonary fibrosis, but that the lung has such capabilities for recovery. Although the major effector cells may all initially participate in damaging the lung and initiating fibrosis, there is evidence that they may also have the capacity to participate in subsequent repair. Macrophages may initially recruit fibroblasts and stimulate them to proliferate, only to suppress them subsequently. Macrophage production of prostaglandins can lead to suppression of macrophage, neutrophil and lymphocyte responses, thus attenuating tissue injury and the development of fibrosis. Neutrophils may initially release toxic metabolites and enzymes that damage parenchyma. However, there is evidence that they may later play a role in attenuating fibrosis, perhaps through collagenase secretion, or through as yet unknown mechanisms. Lymphocytes may initially participate in a number of damaging ways by secreting chemoattractants for other cells and participating in destructive autoimmune processes. However, there is evidence that subpopulations of T cells may dramatically shift during the course of fibrosis, leading to attenuation of the process. It may thus be useful to consider irreversible pulmonary fibrosis as the end result of a process in which the balance of normal injury/repair mechanisms is disrupted. There is clearly no single "fibrogenic event." Rather, there seem to be a number of places where disruption of balance/repair processes may begin. In diseases of unknown etiology such as sarcoidosis or IPF, loss of control may occur at the genetic level, leading to the destructive alveolitis that is the apparent precursor of fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Vidian nerve resection in chronic hypertrophic non allergic rhinitis: effects on histamine content, number and rate of degranulation processes of mast cells in nasal mucosa.

The effects of Vidian nerve resection on the histamine content, number and rate of degranulation processes of mast cells in the respiratory tract of the nasal mucosa in patients with intractable chronic hypertrophic non-allergic rhinitis (CHNAR) have been investigated at various times after surgery. Preliminary data are also presented on the effects of Vidian nerve stimulation on the same parameters. The Vidian nerve was stimulated during surgery before resection. After neurotomy the histamine content was significantly lower than before but the values became less low with the passing of time. The number of mast cells per microscopic field and their degranulation index were significantly lower after surgery than before it. Stimulation determines a significant reduction in the number of mast cells per microscopic field and a parallel reduction in histamine content. These data establish a relationship between cholinergic activity and secretory response of mast cells and demonstrate a role of the parasympathetic nerve supply in the pathogenesis of CHNAR. The great reduction in the number of mast cells and histamine content also suggests that the parasympathetic nerve supply could play a role in the regulation of histamine synthesis and uptake.

Role of mast cells in experimental tumour angiogenesis.

Although the morphological features of angiogenesis are well documented and many promoting factors are known, the pharmacological mechanisms for the development of new vessels are not understood. Compounds found in platelets and/or mast cells--adenosine diphosphate, 5-hydroxytryptamine, histamine and heparin--caused endothelial cell growth stimulation in vitro: tumour angiogenesis factor did not. These same vasoactive compounds, as well as tumour angiogenesis factor, induced neovascularization on the chick chorioallantoic membrane. The increased vascularity produced by tumour angiogenesis factor was associated with considerable numbers of mast cells. These findings, together with an appreciation of the biochemical armoury of the mast cell and how its products could relate to the morphological steps of angiogenesis, and a realization that known anti-angiogenesis factors could all act through inhibition of mast cell products, strongly implicate the mast cell in the inductive mechanisms of neovascularization.

The role of heparin in angiogenesis.

A series of experiments is described in which: (i) mast cells were found to accumulate at a tumour site before the ingrowth of new capillaries; (ii) heparin released by mast cells increased the migration of capillary endothelial cells in vitro; and (iii) heparin enhanced tumour angiogenesis in vivo. These experiments led to the discovery that protamine and platelet factor 4 are angiogenesis inhibitors. This finding suggests a central role for heparin or related glycosaminoglycans in the growth regulation of capillary blood vessels.

Induction of T cell-independent eosinophilia in mice with polymyxin B and schistosome infection.

This study examined the elevation of blood eosinophil counts in athymic and thymus-intact mice after repeated injections of polymyxin B with and without infection by Schistosoma mansoni. In athymic mice, a modest, comparable eosinophilia occurred after polymyxin B injection or parasite infection alone, or after a combination of both. In thymus-intact mice, polymyxin B injection caused a similar low grade eosinophilia, and schistosome infection produced a much higher level of eosinophilia. The combination resulted in the highest levels during the early weeks after infection; this hyperresponsive phenomenon was most apparent following 5 to 7 weekly polymyxin B injections, and the total eosinophil count approximated that derived by adding the eosinophil counts induced by polymyxin B injections or schistosome infection alone. In spite of the changes in blood eosinophil counts, tissue eosinophilia in the liver revealed no apparent differences. Furthermore, in schistosome-infected and polymyxin B-injected thymus-intact mice, hepatic granulomas reached a maximal size earlier than in mice that were only infected, and there was an over-all reduction in mast cell counts. The findings indicate that a T cell-independent eosinophilia occurs under a variety of circumstances. In athymic mice, it accounts for all peripheral eosinophilia, whereas in thymus-intact mice, it operates independently from the well known T cell-dependent eosinophilia of parasite infections.

Physical urticaria/angioedema: an experimental model of mast cell activation in humans.

Urticaria and angioedema may occur in skin and mucus membranes when mast cells are activated by various physical stimuli, including trauma, pressure, vibration, light, cold, heat, and (in rare cases) water. Experimental challenge of patients with cold-induced and cholinergic urticaria/angioedema in particular provides an in vivo model of mast cell activation in humans. This model synthesizes observations of the evolution of clinical manifestations, histologic analysis of tissue alterations, measurement of mediators released into the circulation, and assessment of leukocyte motility. The model in turn allows a characterization of mediators that exist preformed in mast cell granules or that are generated through interactions with other cell types. Release of these mediators produces a variety of biologic effects, including elaboration of certain enzymes and alterations in venular permeability, smooth muscle contraction, leukocyte motility, and the release of substances from other cell types.