Histamine release caused by anti-IgE, specific antigens and calcium ionophore A23187 was examined in leukocyte suspensions from healthy individuals and patients allergic to house dust mite and birch pollen. Staphylococcus aureus and LPS from Salmonella typhimurium were found to cause a synergistic enhancement of the release. The potentiation of mediator release by the bacteria and the endotoxin depends on a binding to the basophilocyte, followed by a non-transient event, since the potentiating effect persists after preincubation of the cells with the LPS followed by washout and leaving the cells for 30 min at 37 degrees C before stimulation with anti-IgE. The potentiation was abolished or reduced by galactose (10(-7) and 10(-6) M) and N-acetylglucosamine (10(-6) and 10(-5) M), acting by a binding to the basophil cell membrane, demonstrated by the persistence of effect after preincubation and washout of unbound sugar.
Microbial content in dusts such as bacteria, endotoxins and fungal spores are thought to be important causative agents for the symptoms in organic dust‐related diseases. Micro‐organism‐induced mediator release was therefore examined in human cells. Bacteria were found to trigger the release of histamine and leurotriene B4 from bronchoalveolar cells, and in suspensions of dispersed lung and tonsillar cells they induce the release of histamine and prostaglandin D2. Basophil histamine release was triggered by both bacteria and their endotxins. Furthermore, histamine release caused by allergic as well as non‐allergic reactions was enhanced by bacteria, endotoxins and fungal spores of mould. These effects of dust components may be crucial for the symptoms in q a n i c dust‐related diseases, since the mediators are of key importance to the broncho‐obstructive and inflammatory events in these disorders.
Histamine release from human basophil leukocytes from allergic patients or controls was induced by specific antigens, anti-IgE or calcium ionophore A23187. Influenza A virus, S. aureus and lipopolysaccharide from S. typhimurium increased the maximum release of histamine and caused a shift to the left of the dose-response curves showing increased cell sensitivity and lowering of the threshold to these stimuli. The mechanism of action was elucidated by examining the mediator release as a function of increasing extracellular concentration of calcium. In these experiments the dose-response curves were changed by the microorganisms and lipopolysaccharide as before. This indicates that the microorganisms and lipopolysaccharide change the basophil cell response to IgE-dependent and non-immunological stimuli by causing a change in the subcellular handling of calcium.
Preliminary studies in hematological patients have indicated that treatment with rhG-CSF reduces basophil releasability ex vivo. We examined this phenomenon further, in allergic patients. Ten patients with grass pollen rhinoconjunctivitis were given rhG-CSF (5 micrograms/kg/day s.c.) for 5 days, and examined before and after treatment. Basophil counts increased from 5 to 19 x 10(9)/l (P < 0.01). Total blood histamine increased from 80 to 160 micrograms/l (P < 0.01), corresponding to a decrease in average basophil histamine content from 1.5 to 0.81 pg/cell (P < 0.01). Isolated mononuclear cells showed a significantly decreased histamine release (HR) when stimulated with A23187 and grass. Whole blood experiments showed a similar decreased HR to grass and anti-IgE (P < 0.01). However, we found an increase in total blood histamine. We conclude that treatment with rhG-CSF (1) increases the number of circulating blood basophils, (2) reduces the average histamine content per basophil, and (3) reduces the basophil releasability. These findings could be due to the mobilization of immature basophils from the bone marrow.
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