Induced Splenocyte Proliferation Research Articles

Centrally injected nerve growth factor modulates peripheral immune responses in the rat.

The effect of the intracerebroventricular (icv) and intravenous (iv) injection of nerve growth factor (NGF) on peripheral immunity was studied in the rat. Icv administration of NGF (5, 25, 50, 250 and 500 ng/rat) significantly enhanced phytohemagglutinin (PHA)-induced splenocyte proliferation 30 min after treatment. Icv pretreatment with an anti-NGF antibody completely prevented the effect, while iv injection of anti-NGF antibody did not block the effect of icv NGF. On the contrary, NGF at doses of 0.5, 2.5, 5, 25 and 50 ng/rat decreased splenocyte natural killer (NK) activity. When injected iv, NGF enhanced splenocyte proliferation only at doses of 50 and 500 ng/rat, while it did not affect NK activity. These effects on immunity do not appear mediated by activation of the hypothalamus-pituitary-adrenal axis, since NGF did not modify plasma corticosterone concentrations at the doses used. These results indicate that NGF participates in the complex network of neuroimmune interactions.

Effect of prostaglandin E 2 and other intracellular cyclic AMP elevating agents on the mitogen induced mouse splenocyte proliferation in a serum free culture condition

Prostaglandins (PGs) play an important role in the regulation of the host's immune responses to infection and inflammation. However, the mechanisms through which the PGs regulate immune functions are not well known. In the present study, we investigated the T cell specific mitogen Concanavalin A (Con A) induced mouse splenocyte proliferation in a serum free condition in vitro in the presence or absence of different doses of PGE 2, indomethacin, cholera toxin and forskolin. The Con A induced splenocyte proliferative responses were significantly inhibited following the addition of PGE 2 and were markedly enhanced in the presence of indomethacin (PG synthase inhibitor). As with PGE 2, both cholera toxin and forskolin, which increase intracellular cyclic AMP by activating stimulatory GTP binding protein (Gs protein) and adenylate cyclase respectively, inhibited splenocyte proliferation in a dose dependent manner. These data indicate that PGE 2 down regulated mitogen induced splenocyte proliferation and that blocking the production of endogenous PGs potentiated T-cell mitogen response. Further, these findings suggest that PGE 2 regulation of splenocyte proliferation is due to increasing intracellular cAMP through G protein transmembrane regulation of adenylate cyclase. This study also provided a defined experimental model to investigate mechanisms of the regulation of cellular function through the exogenous and endogenous mediators such as PGs and their intracellular signal transductions.

Suppression of phytohemagglutinin induced splenocyte proliferation during concurrent infection with Eimeria nieschulzi and Nippostrongylus brasiliensis.

Results suggest that infection with Eimeria nieschulzi (Protozoa) interferes with splenocyte proliferation induced by infection with Nippostrongylus brasiliensis (Nematoda).

Biological effects of Pseudomonas aeruginosa exotoxin A: lymphoproliferation of T lymphocytes in athymic mice.

Pseudomonas aeruginosa exotoxin A has been observed to exert modulatory effects on the immune response. The present study examines the ability of exotoxin A to induce proliferation of splenocytes from athymic nu/nu mice. We observed that exotoxin A induced the proliferation of athymic nude splenocytes which could be abrogated by heating the toxin at 70 degrees C or by preincubation of the toxin with rabbit anti-exotoxin A antiserum. Photoaffinity-labelled toxin significantly induced splenocyte proliferation although the relative activity was reduced. Maximum nude splenocyte proliferation was observed at a toxin dose of 100 ng. This same dose was shown previously for athymic splenocytes to induce an enhanced response to the thymus-dependent (TD) antigen, sheep red blood cells (SRBC). The increased [3H]-TdR uptake in athymic splenocytes stimulated by exotoxin A was initiated by 24 hours and continued to day 10. Nude splenocytes depleted of Ig+ and Ia+ cells were induced to proliferate by exotoxin A. Cyclosporin A addition abrogated the ability of exotoxin A to induce proliferation. These results suggest that Pseudomonas aeruginosa exotoxin A can stimulate the proliferation of splenic T lymphocytes in athymic nu/nu mice.