Biomedical subjects
Publications and source records attributed to G A Belokrylov.
The results of NBT test correlated with the index of phagocytosis completeness in only 43% of 21 clinically healthy volunteers. The level of the lysosomal-cationic test was significantly reduced only if the phagocytosis completeness index was markedly decreased. The latter is an integral value reflecting the bactericidal activity of granulocytes.
In experiments on mice and the influence in vitro of the dipeptides GluTrp, LysAsp, LysVal, AspGlu, GluAsp on their constituent amino acids and mixtures on the indexes of specific and non-specific resistance was studied. There is no difference between the dipeptides and their constituent amino acids (excepting Lys) neither in immune, phagocytosis modulating or antitoxic properties. Some amino acids (aspartic acid, glutamic acid, methionine and tryptophan) are promising for the effective prevention of diseases that develop as a result of chronic benzene intoxication.
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The influence of amino acids, their mixtures, and peptides on the immune response, phagocytosis in vitro, and in CBA mice, and broiler chickens, as well as on in vitro ability of listed preparations to protect animals' splenocytes from toxic action of benzene and aflatoxin B1 were studied. It was shown that amino acids (Asp, Glu, Val, Trp), amino acid mixtures (cerebrolysine, levamine, aviamine), and the dipeptides GluTrp and LysAsp stimulate the immune response to SRBC at subcutaneous and peroral application. The peptides thymopentin, thymosin alpha-1, and peptide mixtures (thymosin fraction 5, thymalin) stimulate the immune response only at the site of subcutaneous injections. Lys, Tyr, and bursin (LysHisGly-amide), regardless of the mode of application, do not change, but Arg inhibits the immune response. None of the preparations studied change the immune response to Viantigen. Levamine, cerebrolysine, and aviamine are immunoreactive only at low doses (6.5 x 10(2)-6.5 x 10(-8) mg/kg). At a dose of 65 mg/kg these preparations lose immunostimulating properties. Amino acids (6.5 x 10(-2) mg/kg), which stimulate, rather than influence or inhibit the immune response, enhance phagocytosis of S. aureus by granulocytes, regardless of mode of application. Levamine and cerebrolysine in the range of doses of 6.5 x 10(-2)-6.5 x 10(-6) mg/kg do not influence phagocytosis; at a dose of 65 mg/kg, phagocytosis is enhanced. Aviamine stimulates phagocytosis as well at low and at high doses. The ability of preparations to protect in vitro at a low concentration (1.3 x 10(-3) mg/ml) murine or chickens' splenocytes from toxic action of benzene and aflatoxin B1 (at 1:1000 dilution) does not correlate with their action on the immune response and phagocytosis. The protective actions revealed by the following preparations include: (a) stimulating the immune response and phagocytosis (Glu, Asp, Trp, amino acid mixture aviamine, the dipeptides LysAsp, GluTrp, the peptide mixtures thymalin, thymosin fraction 5); (b) enhancing the immune response but not influencing phagocytosis (Met, levamine, cerebrolysine); (c) influencing neither the immune response nor phagocytosis (Gly, Ile). At the same time those preparations (Lys, Arg) that stimulate phagocytosis but influence the immune response in a different way (Lys does not influence; Arg suppresses the response) are inert as antitoxic agents. Antitoxic properties of amino acid preparations levamine, cerebrolysine, and aviamine retain as well in the assays at a rather large (1.3 mg/ml) concentration like their phagocytosis-stimulating properties.
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To elucidate the role of immunoactive amino acids (which are capable of stimulating the immune response) in the peptide regulation of antibody production and phagocytic processes we have studied the influence of some fragments of natural peptides and the amino acids included in them on the thymus-dependent immune response to sheep red blood cells (SRBC) and on the phagocytosis of Staphylococcus by murine peritoneal neutrophils. It has been found that the effects of amino acids, as well as of peptides that they form, on the immune response and on phagocytosis were diverse. Glutamic and aspartic acids, threonine and valine stimulated both the immune response and phagocytosis. Glycine and isoleucine influenced neither the immune response nor phagocytosis, whereas lysine, proline, tyrosine and leucine did not influence the immune response, but enhanced the phagocytic activity of neutrophils. Arginine inhibited the immune response but stimulated phagocytosis. Peptide TTKD section (the fragment 77-80 of murine Thy-1-antigen) contained in C- and N-terminus amino acids (T and D) which stimulated the antibody production and phagocytosis, and lysine (K) which stimulated phagocytosis only, enhanced both processes. Peptides LGIP and PYIK (the fragments 49-53 and 66-69 of murine Thy-1 antigen) which contained both immunologically inert amino acids (L, G, I, P, Y, K) and phagocytosis stimulating amino acids (L, Y, P, K) influenced neither the immune response nor the phagocytic activity of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunostimulating properties of cholecystokinin octapeptide (CCK-8) were evaluated in experiments on adult normal and thymectomized mice, in vitro. It was shown that CCK-8 stimulates IgM-PFC production to SRBC, but does not change the immune response to Vi-antigen. CCK-8 increases the number of Thy-I+ spleen T cells and restores thymus-dependent immune response in thymectomized mice. CCK-8 has no effect on neutrophil phagocytosis activity in vitro. The immunostimulating activity of CCK-8 is related mainly to C-terminal fragment (identical to pentagastrin tetrapeptide) since the N-terminal CCK-8 tetrapeptide displays negligible effect in all tests.
It has been shown that per os introduction of sunflower oil and starch to adult thymectomized mice resulted in reconstitution of the number of Thy-I+ spleen cells similar of the glutamic acid effect. Glutamic acid restored the immune response to sheep red blood cells (SRBC), however, sunflower oil and starch were not effective. The influence of these compounds on the immune response to SRBC in normal and sham-thymectomized mice was different: glutamic acid stimulated it, starch had no influence on the immune response, sunflower oil suppressed it.
The experiments on mice have shown that the in vitro treatment of mouse bone marrow cells with levamin or cerebrolysin (amino acids mixture) increased the number of Thy-1 positive cells and stimulated the in vivo immune response to SRBC. Levamin proved more active. At the same time levamin and cerebrolysin had no effect on the immune response to thymus-independent Vi-antigen.
The effects of some natural polypeptides fragments and amino acids which were incorporated in them on the thymus-dependent SRBC immune response and on the phagocytosis of Staphylococcus by murine peritoneal neutrophils were compared. It was found that the peptides LGIP and PYIK which consisted of those amino acids that stimulated phagocytosis but did influence the immune response (K, P, Y, L) did not change the immune response as well as phagocytosis. The peptides TKPR, TTKD and LGIPE which included those amino acids that were able to stimulate both immune response and phagocytosis (T, E, D) enhanced both activities. Nevertheless the peptide PYIKV containing valine (that stimulated the antibody production as well as phagocytosis) did not effect the immune response but enhanced the phagocytic index. The existence of two immunoregulatory systems--the peptide system and the amino acid one--was suggested.
Using the previously obtained data that amino acids could influence the thymus-dependent immune response, the significance of amino acids in the immunostimulating activity of peptides has been studied. The effect of seven synthetic fragments of murine Thy-1 antigen, non-sulfated cholecystokinin (CCK-8), the two tetrapeptides at the N- and C-terminal fragments of CCK-8, as well as neurotensin (NT) have been investigated. It has been found that both NT and those Thy-1 fragments which consisted of immunologically inert amino acids, did not influence the immune response in mice. CCK-8, its C-terminal fragment and those Thy-1-antigen peptides which contained immunoactive amino acids at C- or N-terminus or both, stimulated IgM-plaque forming cells (PFC) in animals. The N-terminal CCK-8 tetrapeptide showed negligible activity. The possibility of the existence of two independent immunoregulatory systems--one amino acids based and the other dependent upon a sequence of amino acids in the peptide is being discussed.
In experiments on mice and in vitro the influence of neurotensin pentagastrin and thymopentin on the immune response, the phagocytosis of staphylococcus aureus by polymorphoneutrophil leucocytes and enzymatic activity of these cells by NBT-test were investigated. It was shown that neurotensin and thymopentin increase enzymatic and phagocytic function of polymorphoneutrophil leucocytes. Pentagastrin, as well as thymopentin stimulates the immune response, enzymatic but not phagocytic function of polymorphoneutrophil leucocytes. Immunostimulating effect of the studied peptides was realized by facility differentiation of mouse bone marrow cells into T-lymphocytes and by the interaction of the peptides with T-cells.
It has been shown that subcutaneous injection of pentagastrin to mice in doses 0.01-5 micrograms per animal during 10 days resulted in a considerable stimulation of the immune response to sheep red blood cells (SRBC). Pentagastrin in doses of 5 and 1 micrograms per animal was demonstrated to have the highest immunostimulating effect. These doses increased the production of IGM-antibody-forming cells 2.2-2.7-fold and produced a twofold elevation of the antibody titer. Pentagastrin did not influence the immune response to thymus independent Vi-antigen. The in vitro treatment of mouse bone marrow cells with pentagastrin (0.1 or 0.01 microgram/ml) increased the number of Thy-1 positive cells from 0 to 16-17%. Pentagastrin at a dose of 0.001 microgram/ml was not effective.