Control of Allergen-Induced Histamine Secretion by Human Basophils with F(ab) of Anti-IgE Antibodies.

A strategy was developed to obtain univalent F(ab) fragments against IgE, which would interfere with IgE-mediated activation of target cells, but lacked their activity due to cross-linking of IgE bound to Fc(epsilon)-receptors. Two kinds of mouse anti-human IgE monoclonal antibodies (mAb) against CH(2) or CH(3) domains induced histamine release from basophils of allergic patients and healthy donors. F(ab')(2) fragments of the mAb (0.01 - 10.0 &mgr;g/ml) possessed the same activity. On the contrary, F(ab) fragments of the mAb did not activate basophils, but in concentrations up to 10.0 &mgr;g/ml they inhibited, both in direct and cross reaction, histamine secretion induced by anti-IgE mAb and their F(ab')(2) fragments. Allergen-induced histamine release from basophils of pollen-sensitive patients was also inhibited by F(ab) fragments of anti-IgE mAb. It was suggested that univalent F(ab) fragments of anti-IgE mAb binding to cell-fixed IgE molecules modified their allergen-induced conformation and, as a result of that, inhibited mediator release from the cells.

Histamine releasing activity of blood mononuclear cells is acquired by means of activation of mast cells.

It has been shown that peripheral blood mononuclear cells (PBMC) obtained from atopic patients with acute clinical manifestations of pollinosis, atopic dermatitis or bronchial asthma, and preincubated in vitro for 18 hours, acquired the ability to induce histamine release from auto-basophils and basophils of healthy donors. Both PBMC and their supernatants possessed this histamine releasing activity (HRA). During remission, HRA could be reproduced in sensitive patients after positive cutaneous tests with a specific allergen. Skin tests with non-specific allergen or histamine-induced provocations were ineffective. HRA of PBMC was also reproduced in healthy individuals after pronounced Prausnitz-Küstner reactions or compound 48/80-induced inflammatory responses. It is concluded that the in vivo activation of mast cells (MC) might be responsible for the acquirement by PBMC of the potential ability to induce histamine release and that this ability was realized after in vitro incubation of such prepared PBMC.

Mast cell regulatory effect on lymphoid cell proliferation.

It has been shown rat mast cells (MC) can modulate lymphocyte proliferation in vitro. Depending on concentrations tested both serosal MC and their supernatants enhanced the spontaneous and T-mitogen-induced proliferation of spleen and lymph node cells. In addition T-mitogen-induced thymocyte proliferation was also increased. The enhancing effect of MC on lymphoid cell proliferation appeared after MC and lymphocytes were cocultured for 24, 48 or 72 h. The highest enhancing action of MC was observed when MC and lymphocytes were plated simultaneously. In contrast, when MC were added 24 or 48 h after the start of lymphocyte culture, the enhancing action of MC decreased or was abolished, respectively. No dependence was found between histamine concentration in MC supernatants and the enhancing activity of supernatants. After chromatographic separation of MC supernatants the fractions with molecular weights between 1-6 KDa augmented lymphoid cell proliferation.