Histamine-induced suppressor factor (HSF): effect on migration inhibitory factor (MIF) production and proliferation.

Histamine added in vitro to cultures of sensitized lymphocytes suppresses antigen-induced production of migration inhibitory factor (MIF) and proliferation by these cells. Recent studies have suggested that lymphocytes bearing histamine type-2 receptors play a regulatory role in these in vitro responses. The present studies were undertaken to determine if suppressor function by cells having histamine receptors was mediated through a soluble product. It was found that lymph node cells from nonimmune or immune strain 2 guinea pigs elaborate a nondialyzable factor into the culture supernatant when incubated with 10(-3) to 10(-5) M histamine (histamine-induced suppressor factor of HSF). HSF, when cocultured with sensitized lymphocytes, suppressed their MIF and proliferative responses to antigen. HSF was made by lymphocytes but not macrophages. Its production could be blocked by an H2 receptor antagonist (burimamide) but not an H1 receptor antagonist (chlorpheniramine). Furthermore, the inhibitory effect of HSF was reversible as lymphocytes washed free of the factor after 24 hr and recultured with fresh medium and antigen were able to produce MIF. Gel filtration by Sephadex G-100 chromatography indicated that HSF had an approximate m.w. of 23,000 to 40,000. These results suggest that the release of histamine at the sites of immediate hypersensitivity reactions, possibly by generating HSF activity, may play a regulatory role in the subsequent development of cellular-immune reactions at the same site.     

Amine dependence of proliferative activity in two transplantable lines of mouse colonic carcinoma

Serotonin, histamine and their antagonists have previously been shown to influence both the cell proliferation rate and the volumetric growth rate of colonic tumours. Of these earlier studies, those on cell proliferation could not distinguish between direct effects on tumour cells and indirect effects on the host, whereas those on the volumetric growth rate of tumours, whilst suggesting an outcome related to the individual properties of the tumour rather than the host, could not distinguish between influences on cell gain, cell loss or stromal changes. In an attempt to distinguish between these possibilities the current experiments on the mitotic rate in two lines of transplantable mouse colonic carcinoma were undertaken. One line of tumour proved to be sensitive to inhibition by a histamine H2 receptor antagonist and a dopamine D2 antagonist but resistant to serotonin antagonists; the inhibition by histamine antagonists was surmountable by co-administration of histamine. The other line proved to be highly sensitive to the inhibitory effects of serotonin antagonist and less so to antagonists of the other two amines and in this case the effect of serotonin antagonists was surmountable by serotonin. These results suggest that the variations between different colonic tumours in the response to amine antagonists is due to differences in the extent of inhibition of cell proliferation rather than differences in cell loss or stromal effects. Thus it appears likely that amine antagonists are able to directly interfere with the proliferation of some colonic tumour cells.     

Modulation of granulomatous hypersensitivity. V. Participation of histamine receptor positive and negative lymphocytes in the granulomatous response of Schistosoma mansoni-infected mice

The possible role of histamine and histamine-receptored inflammatory cells in the granulomatous response of Schistosoma mansoni-infected mice was examined. Special staining revealed the presence of numerous mast cells, many partially degranulated within the liver granulomas. Treatment of infected mice with cimetidine (an H2 receptor antagonist) enhanced, and diphenyhydramine (an H1 receptor antagonist) decreased the granulomatous response. Fluorescein-labeled histamine-rabbit serum albumin conjugate (H-FRSA) and unlabeled conjugate (H-RSA)-coated culture plates were used to identify and isolate cells with histamine receptors. A large proportion of granuloma macrophages, lymphocytes, eosinophils, neutrophils, and splenic lymphocytes had histamine receptors. Elution of adherent cells from H-RSA-coated culture plates with H1 or H2 receptor antagonists suggested that receptors on granuloma cells were predominately H1 with some granuloma lymphocytes bearing H2-type receptors. Splenic lymphocytes from infected mice were functionally divided according to the presence or absence of histamine receptors on their cell surface. Receptor-negative lymphocytes appeared to mediate SEA-stimulated MIF production (TDH cells) and participated in the adoptive transfer of suppression of granulomas (TH cells). Whereas, TS cells appeared to have histamine receptors. Based on these data, it is inferred that lymphocytes that regulate lymphokine production (TS cells) within the granuloma may be triggered via their histamine receptors to exert suppressive activity.     

Response of human fetal lymphocytes in xenogeneic mixed leukocyte culture: Phylogenetic and ontogenetic aspects

Cells from liver, thymus, and spleen of human fetuses at different stages of development were capable of a proliferation response against xenogeneic and allogeneic lymphocytes. The kinetics of fetal responses against rat lymphocytes were identical to those of fetal and adult responses against allogeneic cells. With all of the cell types studied, including adult lymphocytes, allogeneic responses were stronger than xenogeneic. Xenogeneic responses against lymphocytes from rat, mouse, or sheep were stronger than those against lymphocytes from rabbit, chicken, snake, or frog. These results are interpreted to indicate that recognition of foreign lymphocytes by human lymphocytes depends on the phylogenetic position of the species used as a source of stimulating cells. The degree of recognition decreases as the phylogenetic distance increases. Specific elimination of responding cells and restimulation with another cell population was used to study the specificity of proliferation responses against mouse and rat lymphocytes. Responses by prethymic liver cells from human fetuses were not due to the existence of specifically recognizing subpopulations. Thymus and spleen at 16 weeks' gestation contained specific subpopulations capable of differentiating between xenogeneic and allogeneic cells, as well as between xenogeneic cells with different intraspecies histocompatibility patterns. Generation of receptor diversity on T lymphocytes is discussed briefly in the light of these findings.     

Inhibition of normal lymphocyte responses by cell membranes

Cell membranes bearing the appropriate antigen are known to stimulate a variety of cell-mediated immune responses. This report confirms that tumor cell membranes at doses of 2-5 micrograms protein/ml will stimulate in vitro generation of allogeneic cytotoxic T lymphocytes (CTL). However, higher doses (50-100 micrograms protein/ml) of the same membranes completely abrogate the generation of lytic activity. Responding lymphocytes are inhibited by membranes from either syngeneic or allogeneic cells. The inhibition appears to act at a proliferative or differentiation step in the generation of the CTL response, since membranes are known to have little direct effect on the lytic phase of CTL activity. Similar doses of membranes also inhibit LPS-induced B-cell proliferation. B-Cell proliferation is inhibited equally well by allogeneic and syngeneic membranes, and membranes from normal spleen cells are as inhibitory as tumor cell membranes. The inhibitory activity copurifies with the plasma membrane. The results raise important considerations regarding the use of subcellular forms of antigen in studies of lymphocyte recognition. In addition, these data suggest that cell-cell contacts might provide signals regulating the proliferation of lymphocytes.     

Modulation of cellular immune function in vitro by histamine receptor-bearing lymphocytes: mechanism of action.

When soluble histamine is added to guinea pig lymphocytes in vitro, antigen-induced cellular proliferation and the production of migration inhibitory factor is suppressed. The inhibitory effects that are produced by histamine have been shown to be mediated by the histamine-type 2 receptors of the involved cells, but the exact nature of this suppression has not been fully explored. The present studies have evaluated, following immunization, the effect of histamine on macrophage function in vitro, and affinity chromatography to delete a subpopulation of cells bearing histamine receptors. When we treated monolayers of peritoneal exudate cells with histamine (up to 10^?3M) we found that histamine did not interfere with antigen binding by macrophages, macro phage presentation of antigen to lymphocytes, nor the antigen-independent or antigen-dependent lymphocyte-macrophage rosetting. Columns containing insolubilized conjugates of histamine and rabbit serum albumin depleted a subpopulation of cells responsive to histamine i.e., the non-adherent cells made migration inhibitory factor and proliferated in the presence of histamine. The latter finding suggested that the retained cells might have suppressor function and if so, might mediate their effect through the release of a soluble factor. Preliminary data obtained in these studies supports this hypothesis. We conclude that cells bearing histamine receptors may serve a regulatory role in cellular immunity after their activation by histamine by producing a non-dialyzable factor with immunosuppressive properties.     

Properties of histamine-induced suppressor factor in the regulation of lymphocyte response to PHA in mice

Splenic T lymphocytes release a suppressor factor into the culture supernatant when incubated for 24 hr with histamine (10^?4M). Histamine-induced suppressor factor (HISF) inhibits lymphocyte response to PHA; it is released by T lymphocytes (either nylon-nonadherent or nylon-adherent lymphocytes) and not by B-cells or macrophages; its production is not observed after depletion of histamine receptor-bearing lymphocytes and is blocked by the H2 receptor antagonist (cimetidine) but not by the H1 receptor antagonist (diphenhydramine). Gel filtration by Sephadex G100 chromatography indicates that HISF had an approximate MW of 45,000 to 68,000. Its inhibitory activity was removed by passage over a histamine RSA-Sepharose column, but not by passage over rabbit anti-mouse Ig-Sepharose column; it was blocked by prostaglandin synthetase inhibitor (PGS) (Ro 205720) indicating that this activity is mediated by a prostaglandin (PG) synthesis.     

组胺对大鼠小脑皮层浦肯野细胞的兴奋作用

在离体大鼠小脑脑片上观察了组胺对小脑皮层第Ⅹ小叶浦肯野细胞的作用。组胺（３～１００μｍｏｌ／Ｌ）主要引起浦肯野细胞的兴奋反应（９４４％,５１／５４）,在少数细胞上也观察到组胺所引起的放电抑制现象（５６％,３／５４）。用低Ｃａ２＋／高Ｍｇ２＋人工脑脊液灌流脑片,不能取消浦肯野细胞对组胺的兴奋反应（ｎ＝４）。Ｈ２受体对抗剂ｒａｎｉｔｉｄｉｎｅ（０１～５μｍｏｌ／Ｌ）能够阻断浦肯野细胞对组胺的兴奋反应（ｎ＝２０）,而Ｈ１受体对抗剂ｔｒｉｐｒｏｌｉｄｉｎｅ（０５～５μｍｏｌ／Ｌ）不能够（ｎ＝９）或仅轻微地（ｎ＝４）阻断浦肯野细胞对组胺的兴奋反应。这些结果提示,组胺可能主要通过Ｈ２受体的介导对浦肯野细胞起兴奋性调节作用,下丘脑小脑组胺能神经通路可能参与了小脑的某些躯体的和非躯体的功能调节。     

Different h2 receptor antihistamines dissimilarly retard the growth of xenografted human melanoma cells in immunodeficient mice

Melanoma cells and tissues contain considerable amounts of histamine and express histamine receptors, suggesting the existence of autocrine and paracrine regulation by histamine. Our previous in vitro results suggested that histamine elevates melanoma cell growth through the H2 receptor. In this work we show that in vivo tumour proliferation in immunodeficient mice xenotransplanted with a human melanoma cell line is diminished by cimetidine, an H2 receptor antagonist, if combined with a tamoxifen derivate acting on cytochrome p450 molecules (DPPE). Ranitidine, another H2 receptor antagonist, has a weaker inhibitory effect, the kinetics and mechanism of which is probably dissimilar to that of the cimetidine/DPPE mixture.     

Immunological Properties of TtT/M-87 Cell Line Established from Murine Pituitary Tumor-Associated Macrophages

TtT/M-87 cell is a macrophage cell line established from thyrotropic pituitary tumor tissues in mouse. In this paper, we report the immunological properties of M-87 cells as a model of tumor-associated macrophage. Contrasting with resident peritoneal macrophages, M-87 cells constitutively secreted small but significant amounts of TNF-α and IL-1α, which were detectable in both biological assays (cytotoxic activity for L929 and co-mitogenic activity for Con A-induced T cell proliferation, respectively) and ELISA, and produced larger amounts of these cytokines upon stimulation with LPS. They expressed MHC class II molecules on their cell surface without stimulation by IFN-γ. The accessory or antigen-presenting cell activity in antibody-producing response of spleen lymphocytes to sheep red blood cells was shown to be much higher in M-87 cells than normal peritoneal macrophages. In addition, when normal spleen lymphocytes were cultured with allogeneic tumor cells, such as EL-4 and S-180, in the presence of M-87 cells, lymphocytes reactive to stimulator cells were activated to manifest inhibitory effect on the tumor cell growth and also to manifest specific cytotoxic effect on the allogeneic tumor cells. These results show that M-87 cells derived from tumor-associated tissue are activated macrophages and that they are inhibitory to tumor cell growth and augmentative in the induction of T-cell-mediated immune responses.     

Binding of histamine- and other ligand-conjugated macromolecules to lymphocytes

The presence of histamine receptors on lymphocyte membranes was investigated using conjugates of histamine and macromolecules tritiated or iodinated with I-125. Histamine-RSA conjugate binds to lymphocytes and causes patching and capping of the bound conjugate. It was found, however, that free histamine did not inhibit the binding of histamine-rabbit serum albumin to mouse lymphocytes, nor did His-RSA interfere with the binding of free histamine. In addition conjugates between RSA and other small molecules, such as ethylamine, ethanolamine, tyramine and glycine, were found to bind to the same sites on lymphocyte membrane as did His-RSA. Ethylamine-RSA like His-RSA when coupled to Sepharose, was capable of removing antibody producing cells from spleen cells of mice immunized against sheep red blood cells. In addition, when spleen cells from such immunized mice were passed through ethylamine or histamine-RSA-Sepharose and the unbound cells were subsequently injected into X-irradiated mice, a 1.8 fold increase in the immunological response was noted. We conclude that the selective binding to lymphocytes of the various ligand-macromolecular conjugates may be due to some general properties of the cell membrane and not to any specific receptors. Nevertheless, these conjugates can be used as a tool to remove selectively antibody producing cells as well as some regulatory cells.     

New role for histamine in interleukin-3-induced proliferation of hematopoietic stem cells

This study investigated the effect of histamine generated by murine bone marrow cells in response to IL-3 on one particular biological activity of this growth factor, i.e., triggering of cells forming colonies in spleen (CFU-S) into S phase. Evidence is provided that i) IL-3-induced day-8 CFU-S cell cycling, evaluated by hydroxy-urea suicide, is completely abrogated when the binding of histamine to its H2 receptors is blocked by the specific antagonist oxmetidine, whereas cetirizine, a H1 receptor antagonist, is ineffective; and ii) the entry of day-8 CFU-S into S phase in response to IL-3 is likewise abolished when the histamine synthesis promoted by the growth factor is prevented by alpha-fluoromethylhistidine, a specific inhibitor of the histamine-forming enzyme, histidine decarboxylase. Similar results are obtained with both drugs, when a progenitor-enriched bone marrow population is used instead of total cells. Furthermore, i.v. injection of recombinant (r)IL-3 results within 2 hr in a substantial increase in bone marrow cell histamine synthesis together with triggering of day-8 CFU-S into cycle, the latter being completely abolished by a simultaneous injection of the H2 histamine receptor antagonist oxmetidine. Thus, our findings support the notion that both in vitro and in vivo the proliferation of early CFU-S in response to IL-3 is modulated by histamine via its H2 receptors. This conclusion is also consistent with the observation that dimaprit, a specific agonist of these receptors not only enhances the sensitivity of day-8 CFU-S to HU after a 2 hr incubation with bone marrow cells but also increases, to the same extent as IL-3, the number of colonies formed in irradiated spleens after a 5 hr pretreatment.     

Histamine excites rat cerebellar granule cells in vitro through H1 and H2 receptors.

The effects of histamine on the firing of cerebellar granule cells were investigated in vitro. Histamine predominantly produced excitatory (117/123, 95.1%) and in a few cases inhibitory (6/123, 4.9%) responses in granule cells. The histamine-induced excitation was not blocked by perfusing the slice with low Ca2+/high Mg2+ medium, supporting a direct postsynaptic action of histamine. The H1 receptor antagonists triprolidine and chlorpheniramine significantly diminished the histamine-induced excitation, but the H2 receptor antagonist ranitidine did not significantly reduce the excitation. On the other hand, the H2 receptor agonist dimaprit could elicit a weak excitation of granule cells. This dimaprit-induced excitation was blocked by ranitidine but not triprolidine. These results reveal that the excitatory effect of histamine on cerebellar granule cells is mediated by both H1 and H2 receptors with a predominant contribution of H1 receptors. The relevance of these findings to the possible function of the hypothalamocerebellar histaminergic fibers in cerebellum is discussed.     

Inhibition of human skin fibroblast proliferation by histamine and phorbol esters is mediated by protein kinase C

The proliferation of human skin fibroblasts in culture was examined using a [3H]thymidine incorporation assay. Histamine inhibited thymidine incorporation with an IC50 of about 0.2 microM. This effect was blocked by the H1 receptor antagonist mepyramine but not by the H2 receptor antagonist cimetidine. Protein kinase C activators, including several phorbol esters and mezerine, also inhibited thymidine incorporation. The IC50 for beta-phorbol 12,13-didecanoate was less than 0.1 nM. The alpha-isomer of this compound was inactive. Long-term treatment of cells with the beta-isomer eliminated the ability of both histamine and phorbol ester to inhibit thymidine incorporation, presumably due to downregulation of protein kinase C. Our results suggest that histamine H1 receptors are linked to activation of protein kinase C and that activation of this enzyme leads to an inhibition of cell proliferation.     

Differential inhibition of human T-lymphocyte activation by maleimide probes

Cellular thiols are known to be involved in lymphocyte activation, differentiation, and growth. In theory, alkylation of selective cellular thiols could be used to regulate specific processes in the activation sequence by inactivating particular enzymes or structural proteins, although to date specific alkylating probes have not been reported. N-Ethylmaleimide (NEM) is a lipophilic sulfhydryl-alkylating agent that is known to block the in vitro proliferative response of T lymphocytes. NEM (10 microM) was found to be fully inhibitory in PHA, Con A, and MLC assays only when added prior to or simultaneously with the mitogens or allogeneic cells; the addition of NEM only 15 sec after stimulating the cells with PHA resulted in a loss of greater than 50% of the inhibitory activity. The addition of 50 microM 2-ME 10 min after treating the cells with NEM failed to block the inhibitory effect. NEM (10-20 microM) had no adverse effect on lymphocyte viability, but completely blocked lymphocyte agglutination in response to mitogens or allogeneic cells. The lymphocytes overcame the inhibitory effects of NEM after 48 hr in both the PHA and MLC experiments. Resumption of the proliferative response was associated with the onset of agglutination in the PHA assay. In experiments using various analogs of NEM, we noted that the presence of a nonpolar N-linked side group was necessary for inhibitory activity. Pretreatment of PBMC with NEM decreased the total cellular thiols by 50% and blocked proliferation by 99%, whereas N-hydroxymaleimide decreased the total cellular thiols by 38% but had no effect on the proliferative response. The additional 12% of the cellular thiols that react with NEM, but not NHM, account for the inhibitory effect of NEM on lymphocyte proliferation. These findings suggest that selective cellular thiols are critical for T-cell activation.     

Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance

Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU(10)/spleen) while the activity of a single NK cell (LU(10)/10(6) cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.     

Histamine-induced suppressor factor inhibition of NK cells: reversal with interferon and interleukin 2

Culture supernatants of lymphocytes stimulated with 10(-3) to 10(-8) M histamine contain histamine-induced soluble suppressor factor (HISSF) that significantly inhibits the natural killer (NK) cell functions of allogeneic lymphocytes. Lymphocytes precultured with increasing concentrations of HISSF showed a dose-dependent suppressive effect on their NK activity. HISSF was not cytotoxic itself and produced suppressive effects on PBL, NK-enriched large granular lymphocytes (LGL), and isolated T cells. Suppression was evident throughout a range of effector:target cell ratios. Production of HISSF was specifically blocked by the H2 antagonist cimetidine, but not by the H1 antagonist clemastine fumarate. Furthermore, H1 and H2 antagonists themselves do not induce production of HISSF. Although HISSF could inhibit the cytotoxicity of LGL, LGL themselves do not produce HISSF. HISSF inhibition of NK activity could be completely reversed by treating effector lymphocytes with recombinant interferon-alpha (IFN) for 1 or 2 hr or culturing them with purified interleukin 2(IL 2) for 36 hr. Our data suggest that exogenous IFN and IL 2 may have therapeutic potential in the treatment of immunological diseases associated with histamine-induced suppressor cell activity.     

In Vitro Reconstitution of Anti-Sheep Erythrocyte Antibody Response of T Cell-Depleted Spleen Cells by Allogeneic T Cells or by Factors Derived from Them

Restoration of the impaired antibody response to sheep erythrocytes (SRBC) in cultures of mouse spleen cells, which were deprived of thymus-derived lymphocytes (T cells) by treatment with anti-mouse brain-associated θ (BAθ) antiserum and complement, was studied by adding a small portion of syngeneic or allogeneic normal spleen cells in vitro. Allogeneic spleen cells had a far greater effect than syngeneic spleen cells on the restoration, as far as the normal spleen cells added were able to recognize the alloantigens on the anti-BAθ serum-treated spleen cells (bone marrow-derived lymphocytes). Treatment of the allogeneic spleen cells with mitomycin C did not affect their activity in the restoration of the impaired antibody response. The possibility that the role of T cells in the antibody response to SRBC may be replaced by a nonspecific mediator derived from T cells reacting with allogeneic cells was proven by the finding that supernatant of the mixed allogeneic spleen cell cultures restored the impaired anti-SRBC antibody response of the T cell-depleted spleen cells. The effect of such culture supernatant on the restoration of the antibody response was greatest when it was added to the T cell-depleted spleen cell cultures one day after cultivation with SRBC, suggesting that the effectiveness may result from triggering of the proliferation and differentiation of antibody-forming cell precursors, which have already reacted with the antigen, to antibody-forming cells.     

Evidence of serotonin-dopamine involvement in the inhibition of d-amphetamine stereotypy and appearance of stereotyped movements found respectively after acute and long-term treatment with morphine and methadone in rats

P-chlorophenylalanine, an inhibitor of serotonin synthesis, was found to completely prevent the inhibitory effect of morphine and methadone on the stereotypy caused by d-amphetamine and methyl-phenidate in rats. d-Fenfluramine and m-chlorophenylpiperazine, two drugs supposed to increase serotonin transmission, and halo-peridol, an antagonist of dopamine at central receptors, blocked the stereotyped movements induced by repeated treatment with morphine and methadone. The results suggest that a) brain serotonin mediates the effect of morphine and methadone on amphetamine and methylphenidate stereotypy b) serotonin and dopamine are involved in the stereotyped movements caused by long-term treatment with these narcotics in the rat.     

Transglutaminase and polyamine dependence of effector functions of human immunocompetent cells: The effect of specific inhibitors on lymphocyte proliferation and granulocyte chemiluminescence

The effects of the transglutaminase inhibitor dansyl cadaverine (DC) and the polyamine antagonist methyl glyoxal-bis-(guanylhydrazone) (MeGbG) on the response of lymphocytes towards allogeneic and lectin stimulation and on the zymosan-induced chemiluminescence of neutrophilic granulocytes was studied. Application of DC resulted in dose-dependent suppression of chemiluminiscence and lymphocyte proliferation; no difference of inhibitory potential occurred with variation of incubation time in the latter system. MeGbG was inactive in granulocytes, but inhibited lymphocyte proliferation; its effect increased with time. The experiments provide further evidence for the importance of transglutaminases and polyamines for the function of immunocompetent cells.