Effect of lysophosphatidylserine on immunological histamine release.

The effect of lysophosphatidylserine on immunological histamine release has been studied in rat peritoneal mast cells actively sensitized with horse serum and in human basophils challenged with anti-IgE. In contrast to other lysophospholipids, lysophosphatidylserine enhances the immunological histamine release in rat mast cells. The effect shows the kinetics of a saturable process with an apparent Km for lysophosphatidylserine of 0.26 microM. A similar Km value (0.21 microM) is found when measuring the non-immunological histamine release activated by lysophosphatidylserine plus nerve growth factor. A comparison with phosphatidylserine shows that a half-maximal response to lysophosphatidylserine occurs at a concentration 4-times lower. In addition, the magnitude of the response is higher. At variance with rat mast cells, lysophosphatidylserine does not influence the histamine release elicited by immunological and non-immunological stimuli in human basophils. The histamine secretion in these cells is instead affected by a calcium ionophore or tetradecanoylphorbolacetate, a compound producing activation of protein kinase C.

Type I reactions directed against Pneumocystis carinii in AIDS patients.

Type I allergy directed against Pneumocystis carinii (PC) has been investigated in 14 patients with AIDS. The Pneumocystis carinii pneumonia often shows a rapid and severe course, and type I allergy against the parasite might be a pathogenic co-factor in the interstitial lung inflammation. In twelve of the AIDS patients the clinical symptoms and course of illness indicated a PC pneumonia. The basophil histamine release test was used as a sensitive test to detect type I allergy against PC. Eight of the patients showed significant histamine release when stimulated with PC. In contrast, only two patients in the group of 12 HIV antibody-positive homosexual men and none in the control group of 13 heterosexual men released histamine. The histamine release was mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins before the antigen challenge. The results suggest an involvement of type I allergy as a pathogenic co-factor in Pneumocystis carinii pneumonia.

The indoor microfungus Trichoderma viride potentiates histamine release from human bronchoalveolar cells.

Trichoderma viride (Tv) is often found in damp and mouldy buildings where people complain of adverse health effects including mucosal/respiratory symptoms. Inhaled spores can reach the alveoli and may interact with the airway epithelium. An interaction with the mucosal mast cells was studied in cells obtained by bronchoalveolar lavage (BAL) from 18 individuals. The fungal spores were found to trigger histamine release from the BAL cells, but relatively high concentrations (0.1-2 mg/ml) were needed. A similar dose response was obtained in basophil histamine release. The Tv-induced mediator release was caused by non-immunological (non-IgE-dependent) mechanisms since the histamine release was not changed by removal of IgE from the basophils before exposure of the cells to the spores. However, in very low concentrations (0.1 ng/ml) the fungal spores were found to potentiate IgE-mediated histamine release triggered by anti-IgE antibody in suspensions of BAL cells. Potentiation was also obtained in basophil histamine release, but relatively high concentrations of Tv (10(-2) mg/ ml) were needed. Our in vitro experiments show that mucosal mast cells from the airways are highly sensitive to the potentiating effect of Tv. Although inhalation studies are needed to determine the in vivo effect of the spores, the results suggest reinforcement of mediator release to be a mechanism in the adverse health implications observed in mouldy buildings.

Basophil-bound IgE and serum IgE directed against Haemophilus influenzae and Streptococcus pneumoniae in patients with chronic bronchitis during acute exacerbations.

The investigation includes 12 patients hospitalized with acute exacerbations of chronic bronchitis (CB) and infected in the lower respiratory tract with Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP). Eight patients were infected the HI, three with SP, and one patient with both species. Basophil-bound IgE and serum IgE directed against these species were examined using the patients' own bacterial isolates. All patients showed IgE-mediated histamine release when their peripheral leukocytes were incubated in vitro with the infecting species, indicating basophil-bound IgE directed against their own bacterium. No IgE-mediated response was obtained in the control group of 12 healthy individuals. Bacteria-specific IgE in serum was demonstrated by immunofluorescence assay and further verified by passive sensitization. There was a positive serum titre in seven of nine patients housing HI and in all SP-infected patients but not in the control group. No synchronism was found between a positive response in the histamine release test and the immunofluorescence assay by parallel testing during the test period. This may be due to a time delay between production of serum IgE and its fixation to the cell surface. The results indicate a potential for a bacteria-specific IgE-mediated immune response in CB. Thus, by triggering mediator release, bacteria may be involved in the pathogenesis of exacerbations in CB.

Chlamydia pneumoniae and possible relationship to asthma. Serum immunoglobulins and histamine release in patients and controls.

Chlamydia pneumoniae (C.pn.) is claimed to be of importance for the development of bronchial asthma in previously healthy individuals. This is a new and speculative theory. Earlier studies have mainly focused on C.pn. and exacerbation of asthma. If this new theory were true, one would expect titres of C.pn.-specific IgG to be higher or more common in patients compared with controls. It would also seem probable that pathobiological mechanisms as found in connection with other microorganisms could be demonstrated, i.e. presence of C.pn.-specific IgE and the capability of C.pn. to induce or enhance histamine release from basophil leukocytes. We therefore examined C.pn.-specific IgE, IgG and IgM in sera from 22 adults with bronchial asthma and 25 healthy controls. IgE was verified by passive sensitization of basophils from umbilical cord blood. The prevalence of IgE was approx. 69% and IgG approx. 23% in both groups. IgG-titres were between 1:16 and 1:64 in both groups. No IgM was found. Further, C.pn. could neither induce nor enhance histamine release from basophil leukocytes of patients or controls. We conclude that patients with bronchial asthma and healthy controls do not differ in relation to 1) C.pn.-specific IgE in sera, 2) the capability of C.pn. to induce or enhance histamine release from basophil leukocytes, since no such effect was found, or 3) previous C.pn. infection judged by the presence of specific IgG antibodies. Our results cannot support the theory that C.pn. is a cause of adult-onset asthma.

Haemophilus influenzae release histamine and enhance histamine release from human bronchoalveolar cells. Examination of patients with chronic bronchitis and controls.

Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae) and Branhamella catarrhalis (B. catarrhalis) are often found in the lower respiratory tract of patients with chronic bronchitis. Earlier studies have shown that bacteria induce mediator release from human basophils and parenchymal lung mast cells. In this study the capability of bacteria to trigger or potentiate histamine release from superficially located mast cells in the airway epithelium was studied in cell suspensions obtained by bronchoalveolar lavage in patients with chronic bronchitis (CB). In approximately half of the patients H. influenzae and Staphylococcus aureus (S. aureus) were found to trigger histamine release, whereas no response was obtained by S. pneumoniae or B. catarrhalis. The mediator release was caused by a non-IgE-dependent mechanism. At lower concentrations of H. influenzae causing no histamine release the bacterium was found to enhance IgE-mediated histamine release triggered by anti-IgE antibody. The synergy was more pronounced in patients with CB than in controls. Since H. influenzae is found in the lower respiratory tract of the patients but not in normal individuals, the infection here may via histamine release lead to harmful effects on the airways of importance for precipitation and exacerbation of chronic bronchitis.

The in vivo and in vitro effects of rhG-CSF on allergic, haematological and biochemical variables.

UNLABELLED: The objective was to evaluate the influence of treatment with rhG-CSF on allergic indexes. This was done by open trial of 5 days' treatment with rhG-CSF (5 microg/kg/day s. c.). 10 patients (6 men), aged 28 to 54 years, with rhinoconjunctivitis due to grass pollen allergy, participated in the investigation. Main measures were blood count, basophil histamine release, skin test and conjunctival provocation test. RESULTS: The treatment resulted in significant increases in numbers of neutrophils (590%), basophils (280%), eosinophils (250%) and lymphocytes (71%). Total blood histamine was increased, but basophil histamine releasability was decreased. Serum alkaline phosphatase increased 92% and serum lactate dehydrogenase increased 35% (both significant). There were no significant changes in the skin tests and the conjunctival provocation tests. Two months after the treatment all tests had returned to baseline levels. Five of the patients (50%) reported side effects, one withdrew. In conclusion treatment with rhG-CSF increases the number of circulating blood cells other than neutrophils without causing changes in indexes of allergic reactivity.

Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load.

Helicobacter pylori is an important pathogen in gastroduodenal inflammation and ulceration. Several mechanisms have been proposed to explain its role. We studied the cytokine production patterns in situ in gastric mucosal biopsies from H. pylori-positive and H. pylori-negative patients with dyspepsia. Immunohistochemistry with monoclonal antibodies was used. The study showed enhanced expression of interleukin (IL) -8, IL-10 and interferon-gamma (IFN-gamma) in H. pylori infection and a significant association was found between these cytokines and the following parameters: bacteria load, chronic inflammation and activity. These parameters were significantly correlated with the cell markers CD19 and CD56. The study indicates a dual effect of H. pylori on the Th1 response, i.e. a stimulation of the response verified by increased IFN-gamma and a feed-back verified by an increase of the counterinflammatory IL-10, which may dampen the inflammatory and cytotoxic effect of the Th1 response. Furthermore, the study confirms the connection between increase of IL-8 and inflammatory activity in gastric mucosa in H. pylori infection.

Examination of serum IgE specific to pig protein in pig farmers by histamine release test.

Pig farmers are susceptible to a number of occupational hazards which may lead to respiratory symptoms. Therefore, inhalation allergy to pig was examined in pig farmers, including 40 farmers with work-related respiratory symptoms and 40 farmers without these symptoms. The presence in serum of IgE specific to pig protein was examined by the histamine release test, based on passive sensitization of basophil leukocytes with the farmers' serum. This test showed pig-specific IgE in a highly selected group of pig farmers in a previous study. In the present study of nonselected farmers, no swine-specific IgE was found in their serum. The results are thus in accordance with previous studies of nonselected populations of pig farmers tested by RAST and skin prick test. It can therefore be concluded that IgE-sensitization to pig protein is not a common phenomenon in pig farmers.

Autoimmune type I reactions directed against nuclear components in rheumatoid arthritis.

Basophil histamine release was examined in leucocyte suspensions from patients with rheumatoid arthritis (RA) after challenge of the cells with isolated and sonicated leucocyte nuclei from normal individuals. Most of the patients with active disease responded with significant histamine release, whereas no response was obtained in the inactive patients and in normal controls. A similar pattern was found in the urinary excretion of the main metabolite of histamine, NT-methyl-imidazoleacetic acid, since an increased excretion was observed in most patients with severe disease activity in contrast to patients with moderate and quiescent activity and the control group. These findings strongly indicate an involvement of autoimmune allergic type I reactions in RA. The release of histamine and other mediators from basophils and mast cells may cooperate in the inflammatory reactions and the destruction of the joints in RA.

[Respiratory tract infection and acute deterioration of obstructive lung disease]. / Luftvejsinfektion og akut forvaerring i obstruktive lungesygdomme.

Respiratory infection may aggravate chronic obstructive pulmonary disease. Viral respiratory infections may aggravate asthma, particularly in young individuals. Respiratory Syncytial virus and Rhinovirus dominate in children while, in adults, Influenza or Rhinovirus infections are most frequently concerned. Viral respiratory infections may also cause exacerbation of chronic bronchitis. Bacteria and their products scarcely play any part in asthmatic disease but may possibly aggravate chronic bronchitis and other forms of obstructive respiratory disease. In particular, Haemophilus influenzae and Streptococcus pneumoniae and bacterial endotoxin appear to be of significance. The mechanisms of the effects of viruses have several points of attack: Destruction of epithelium, release of mediators, potentiation of mediator-release and reduced beta-adrenergic function. Bacteria and their products may, similarly, cause bronchoconstriction and may, in vitro, release mediators and potentiate release of mediators.