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  • 1
    ISSN: 1432-1440
    Keywords: Immune complexes ; i.v.-immunoglobulin preparations ; 7S-IgG ; F(ab')2 ; Fab ; Inflammation ; Side-effects ; Therapy ; Prophylaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies of the IgG class possess antibacterial, antiviral and toxin neutralizing properties and for this reason are administered prophylactically and therapeutically. In the case of the immunoglobulin preparations commercially available for i.v. application a basic distinction must be made between unsplit immunoglobulins and those antibody preparations obtained by enzymatic digestion, such as F(ab')2 or Fab antibodies. This survey deals with the largely experimental evidence describing the biological properties of these preparations. Administration of antibodies in the presence of the corresponding antigens leads to the formation of immune complexes in the organism. These immune complexes can activate, either directly or indirectly, the cellular and humoral systems which are involved in phagocytosis and the elimination of antigens, in the regulation of the body's own antibody production and in inflammatory reactions. As a result of their inability to interact with Fc receptors, immune complexes with F(ab')2 or F(ab) antibodies appear to be less active in the release of inflammation mediators from leucocytes and thrombocytes than immune complexes with unsplit immunoglobulins. These, on the other hand, can antigen-specifically and non-antigenspecifically suppress the immune system which is not the case for immune complexes with F(ba')2 or Fab antibodies. There are indications that these split products also occur in vivo due to the action of tissue and leucocyte proteases. Unlike Fab prcparations, F(ab')2 antibodies have antibacterial and antiviral potencies similar to unsplit immunoglobulins, which is probably due to the ability of F(ab')2 molecules to activate complement, not by the classical but by the alternative pathway. Like Fab preparations, F(ab')2 molecules appear to be superior to unsplit IgG in the elimination of haptens. On account of the relatively long period of time unsplit immunoglobulins remain in the blood, they are well suited for prophylactic treatment and substitution over longer periods. The extent to which indications, obtained predominantly from experimental studies, of a reduced release of inflammation mediators, a lack of immune suppression and a lack of augmentation of IgG catabolism would advocate the use of F(ab')2 split products, especially for therapeutic purposes, can only be ascertained after prospective and comparative studies have been carried out.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Granulocytes ; CSF ; Oxidative metabolism ; Bladder carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neutrophils (PMN) are the major host defence cells protecting the body against invasion by microorganisms. Products of oxidative metabolism mediate PMN microbicidal and tumoricidal activity, but the mechanisms by which these pathways become activated are not well understood. The colony stimulating factors (CSF) are known to stimulate proliferation and differentiation of committed bone marrow stem cells. These regulators may probably play an important role in non specific resistance to infections. We studied the oxidative metabolism of neutrophils after stimulation with recombinant GM-CSF (r.GM-CSF) and the concentrated conditioned medium of the UBC-5637 cell line (UBC-CM) showing CSF activity. It could be demonstrated that the r.GM-CSF, as well as the UBC-CM, induce an activation of the neutrophil respiratory burst without any cofactors such as f-MLP, PMA, or zymosan. In addition, we observed an increase of the response to those stimulants in the presence of either r.GM-CSF or UBC-CM. These effects were not endotoxin-induced, since stimulation persisted after addition of Polymyxin B, which is known to inhibit the action of endotoxins.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: GM-CSF Receptor ; Granulocytes ; Oxidative metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the interaction between GM-CSF and its receptor on human granulocytes and on several human tumor cell lines. Specific high-affinity binding for GM-CSF was characterized by Scatchard plot analysis. The specific radioactivity of the 125I-labeled derivative of rH. GM-CSF was determined by self-displacement analysis and calculated to be 30 μCi/μg. The maximum concentration of binding sites (B max) in granulocytes was 40 fmol/mg protein (2,200 molecules GM-CSF bound/cell) and the dissociation constant (KD) was 0.42 nM. No binding sites for GM-CSF were found in two lung cancer cell lines, SCLC-16HV and NCI-N417 or in the urinary bladder carcinoma cell line 5637, whereas the promyelocytic leukemia cell line HL60 was positive for GM-CSF binding. Time course experiments showed maximum binding of GM-CSF in granulocytes after an incubation period of 60 min and a decrease in binding after an incubation period of 2 h. In parallel, we found a maximum biological signal when granulocytes were preincubated for 90 min with GM-CSF, and a decrease after an incubation time of 120 min. Preincubation of the cells with rH. GM-CSF induced an enhancement of the production of activated oxygen species by the cells in response to PMA.
    Type of Medium: Electronic Resource
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