Multiple Mycobacterium microti derived lipids stimulate iNOS gene expression in the J774 murine macrophage cell line.

The inducible nitrogen oxygen synthase (iNOS) and nitric oxide (NO) system acting in concert with superoxide radicals is recognized as a powerful macrophage microbicidal mechanism. However, experimentation with iNOS knockout mice has rendered contradictory results on the protective role of iNOS/NO in the course of mycobacterial infections. On the other hand, NO also plays an immunoregulatory role. Knowing the nature of the mycobacterial constituents that induce iNOS gene expression would help to better understand the host-parasite relationship. Lipoarabinomannan (LAM) and a 19 KDa lipoprotein are the two known mycobacterial constituents that have shown to induce iNOS. By screening a set of methanol extracted lipids from Mycobacterium microti, here we provide evidence that multiple mycobacterial molecules of lipidic nature both of intermediate and of high polarity, with free amino groups or carbohydrates but no phosphate groups as part of their structure are capable of inducing iNOS gene expression in J774 cells, thus implying a complex relationship between mycobacteria and their host immune system in regard to iNOS gene expression.

Altered pattern of connectivity in serum immunoglobulins from pemphigus vulgaris patients.

Pemphigus vulgaris is a cutaneous autoimmune disease in which the occurrence of autoantibodies directed against desmoglein-3 and other self-antigens has been well established in patient sera. However, V-region interactions (connectivity) of serum IgG and IgM have not been analysed to date. In this report, it has been demonstrated that IgG and IgM in the sera of pemphigus vulgaris patients bind a preparation of F(ab')2 fragments fractionated according to their isoelectric points, and that a pattern of connectivity distinguishable from that of healthy donor sera arises when the sera are tested against 20 individual isoelectric-focusing-separated F(ab')2-containing fractions. This suggests that there are alterations in regulatory networks. In spite of the fact that prednisolone-based treatment of pemphigus patients has proved to be effective in controlling the disease, some undesirable effects associated with this form of treatment have prompted investigation into other therapeutic approaches. One possible approach to the treatment of this autoimmune disease is the use of high doses of normal polyclonal immunoglobulins. In fact there are a few reports of the empirical intravenous administration of immunoglobulins to pemphigus vulgaris patients. The results presented here provide the rational basis for using such a treatment, since it is demonstrated that a deviation from healthy V-region interactions can be attributed to pemphigus patients and that such a condition is considered to be modified by this type of immunotherapy.