Proliferation Of Mouse Spleen Cells Research Articles

Down-regulation of protein kinase C in murine splenocytes: a potential mechanism for 2-acetylaminofluorene-mediated immunosuppression.

2-Acetylaminofluorene (AAF), an arylamide carcinogen, inhibited in a dose dependent manner mouse spleen cell proliferation in response to lipopolysaccharide (LPS). The objective of the present studies was to investigate the effects of AAF on protein kinase C (PKC) activation, an enzyme required for LPS-induced splenocytes proliferation. After treatment with 50 microM AAF for 18 h, PKC activity in the cytosolic fraction decreases by 50% from the control level, and splenocytes lost 30% of total PKC activity. Furthermore, as determined by the electrophoretic mobility shift assay, AAF inhibited the binding activity of the transcription factor complex, NF-KB, whose LPS-mediated induction is dependent on PKC activation in murine splenocytes. These results strongly suggest that LPS-mediated signaling in spleen cells is interrupted by AAF early in the signal transduction pathway, at a point proximal to the activation of PKC.

A synthetic peptide corresponding to 86–93 of the human type I IL-1 receptor binds human recombinant IL-1 (α and β) and inhibits IL-1 actions in vitro and in vivo

A synthetic peptide corresponding to 86–93 of the human type I IL-1 receptor and its analogues bound human recombinant (hr) IL-1 (α and β)and inhibited dose-dependently both Con A-stimulated proliferation of mouse spleen cells andhrIL-1β-stimulated formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in rat bone marrow cell cultures. Furthermore, hrIL-1β-induced mouse paw edema was dose-dependently inhibited by systemic administration (ip) of the synthetic peptide. These results suggest that one of the IL-1 binding sites of the human type I IL-1 receptor comes to the region of 86–93 and the synthetic peptide having the ability to bind hrIL-1 (α and β) blocks the biological activities of exogenous hrIL-1β and endogenous mouse IL-1.

Differences in the effects of the antirheumatic drugs, bucillamine andd-penicillamine, on mitogen-induced proliferation of mouse spleen cells

The effect of bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine], a new antirheumatic drug, on the concanavalin A (Con A)-induced proliferation of mouse spleen cells was compared with the effect of D-penicillamine (D-pen). Bucillamine inhibited the Con A-induced incorporation of thymidine (TdR) into mouse spleen cells in a dose-dependent fashion. At the concentration of 10(-4) M, bucillamine inhibited the incorporation by approximately 80%. The inhibitory effect of bucillamine was not enhanced by the addition of copper. In contrast, D-pen showed the same degree of inhibition only in the presence of copper. (4R)-7,7-Dimethyl-6-oxo-tetrahydro-3H-1,2,5-dithiazepine-4-carboxy lic acid (SA981), an intramolecular disulfide derivative of bucillamine, also showed the same degree of inhibition as bucillamine in the absence and presence of copper, whereas D-penicillamine disulfide did not show the inhibitory effect even in the presence of copper. The inhibitory effects of bucillamine and SA981 were not abolished significantly by the addition of catalase which restored the inhibition by D-pen plus copper. The mechanism of inhibition by D-pen plus copper is believed to involve the production of hydrogen peroxide resulting from the oxidation of D-pen. The results in this study, however, indicated that the inhibitory effect of bucillamine is not due to the production of hydrogen peroxide.

Stimulation of proliferation of murine lymphocytes by the calcium ionophore A 23187 in the absence of serum: The requirement for thiols

The proliferation of mouse spleen cells and T-lymphocytes, initiated by the calcium ionophore A 23187 was studied by a serum-free culture technique. In contrast to Con A, A 23187 was capable of stimulating cells only if 2-mercaptoethanol, cysteine and glutathione (reduced form), respectively, were present in the culture medium. In the absence of one of these compounds a stimulating activity of A 23187 was observed only with high concentrations of cells (i.e., 10 7/ml). With glutathione present, the cells could be stimulated only at concentrations of A 23187 which were found to be suboptimal in cultures with 2-mercaptoethanol. Human serum, fetal calf serum and bovine serum albumin shifted the active and optimally stimulating concentrations of A 23187 to higher values. A similar effect was observed with sera- and Con A-treated cells. The effect of sera and albumin was paralleled by a protecting effect of cells against high concentrations of A 23187.

Mitogenic effects of beryllium and zirconium salts on mouse splenocytes in vitro

The beryllium (Be) and zirconium (Zr) salts, BeSO 4 and Zr(SO 4) 2, each exerted a concentration-dependent stimulation of mouse spleen cell proliferation as measured by an increase in [ 3H]thymidine incorporation into lymphocyte DNA, although the maximal response induced by Zr(SO 4) 4 (4–5 fold at 100–200 μM) was greater than that by BeSO 4 (2–3 fold at 1–5 μM). Preincubation of splenocytes with low concentrations of BeSO 4 (< 1 μM) or a broad range of Zr(SO 4) 2 concentrations (2–100 μM) was also found to assist subsequent lectin (concanavalin A; ConA)-mediated lymphocyte proliferation. The results indicate that at defined concentrations Be and Zr salts can both act as lymphocyte mitogens and augment the functional responsiveness of immune cells, which may help explain the characteristic induction of delayed hypersensitivity and production of immunological granulomas by these metals in vivo.

Anti-immunoglobulin in combination with cytochalasin stimulates proliferation of murine B lymphocytes.

The ability of cytochalasin to influence the stimulation of murine B lymphocytes through surface immunoglobulin was assessed during short term cultures. Modest doses of anti-immunoglobulin alone did not stimulate proliferation of mouse spleen cells at 2 days. Cytochalasin B alone also had no effect. However, anti-immunoglobulin in combination with cytochalasin B stimulated substantial proliferation as judged by [3H]thymidine incorporation. Cytochalasins A, E, and D, and dihydrocytochalasin B were all effective in promoting B cell proliferation. Spleen cells from xid-defective (CBA/N X DBA/2)F1 male mice failed to proliferate in response to anti-immunoglobulin plus cytochalasin, suggesting that this treatment affects the same subset of B cells as anti-immunoglobulin plus B cell growth factor. Moreover, proliferation that was stimulated by anti-immunoglobulin plus cytochalasin B was not affected by T cell depletion. Cytochalasin may circumvent the need for, or replace, a second signal for proliferation.

Effect of carnosine on the immunosuppressive effect of histamine

It has been demonstrated in experiments that histamine is capable of suppressing the antigen-induced proliferation of mouse spleen cells. This histamine effect was suppressed by its H-2 antagonist metiamide but not H-1 antagonist mepiramine. Carnosine exerted an action similar to metiamide, also inhibiting the histamine-caused suppression of murine lymphocyte proliferation. This makes it possible to classify it with the group of H-2-histamine blockers. The H-2-antihistamine properties exhibited by carnosine necessitate its further study as a new antiallergic drug.