calcimycin and Acquired-Immunodeficiency-Syndrome

Spontaneous histamine release and basophil response to IgE-dependent (anti-IgE) and IgE-independent (formyl-methionine peptide, calcium ionophore A23187) stimuli were evaluated in 15 patients with acquired immunodeficiency syndrome (AIDS), 8 with AIDS related complex (ARC), 7 with lymphadenopathy syndrome (LAS), 11 seropositive asymptomatic subjects, 10 human immunodeficiency virus (HIV)-seronegative drug addicts, and 20 normal subjects. Both spontaneous histamine release and anti-IgE-induced histamine release were significantly increased in HIV-infected subjects, in comparison with seronegative drug addicts and normal controls. Basophil response to anti-IgE was higher in AIDS/ARC patients than in seropositive asymptomatic subjects and LAS patients, although the difference was not statistically significant. When basophils were challenged with 0.1 microM formyl-methionine peptide, a significantly increased histamine secretion was found in HIV-infected subjects; conversely, at the higher formyl-methionine peptide concentration (10 microM), as well as at all calcium ionophore A23187 concentrations, histamine release was similar in all the studied groups. No correlation was found among anti-IgE-induced histamine release, total lymphocyte counts, CD4+ and CD8+ T cell counts, and total serum IgE levels. These findings indicate that infection with HIV is associated with an increased basophil releasability. This could be of some relevance in the increased incidence of allergic manifestations and adverse drug reactions observed in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; Basophils; Calcimycin; CD4-Positive T-Lymphocytes; Histamine Release; HIV Infections; HIV Seropositivity; Humans; Immunoglobulin E; Leukocyte Count; N-Formylmethionine Leucyl-Phenylalanine

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.

Topics: Acquired Immunodeficiency Syndrome; Adult; Animals; Calcimycin; Histamine Release; Humans; Immunoglobulin E; Male; Middle Aged; Pneumocystis

We have studied whether the decreased lymphocyte proliferative responses of AIDS lymphocytes to stimulation by mitogens and antigens may be overcome when challenged with a combination of calcium ionophore A23187 and phorbol ester PMA. Comparison of the proliferative response of lymphocytes from nine patients with AIDS with the response of lymphocytes from nine control subjects showed that the response of AIDS lymphocytes was severely decreased when stimulated with PHA and no further response could be achieved by stimulation with A23187/PMA. On the other hand, no significant difference between the PHA-induced rise of cytoplasmic free calcium concentration ([Ca2+]1) in normal and AIDS lymphocytes was observed. The percentage of cells expressing IL-2 receptors (CD25) was also normal both after addition of PHA and after addition of A23187/PMA and the expression was normal on both CD4 and CD8 cells. The production of IL-2 in normal lymphocytes stimulated with A23187/PMA was 33 times higher than that after stimulation with PHA. In AIDS lymphocytes the production of IL-2 induced by all activators was severely decreased compared to control subjects, although the production of IL-2 after stimulation with A23187/PMA was higher than that in control lymphocytes after stimulation with PHA. The present study shows that a direct activation of protein kinase C combined with mobilization of cytoplasmic calcium does not overcome the lymphocyte proliferative deficiency of AIDS lymphocytes.

Topics: Acquired Immunodeficiency Syndrome; Calcimycin; Calcium; Cytoplasm; Humans; Interleukin-2; Lymphocyte Activation; Lymphocytes; Male; Receptors, Interleukin-2; Tetradecanoylphorbol Acetate

The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation.

Topics: Acquired Immunodeficiency Syndrome; Benzofurans; Calcimycin; Calcium; Cell Division; Cytoplasm; Drug Interactions; Fluorescent Dyes; Fura-2; Humans; Interleukin-2; Lymphocytes; Phytohemagglutinins; Plant Extracts; Receptors, Interleukin-2; Spectrometry, Fluorescence; Tetradecanoylphorbol Acetate; Thapsigargin