Mechanisms of tissue injury induced by immune-complexes

RESUMO

Tissue injury induced by immune-complexes (IC) contributes to the pathogenesis of several diseases. The mechanisms by which IC induce lesions are, however, poorly understood. We review here some studies on the role of lipid mediators, eicosanoids and platelet activating factor (PAF), in the development of these lesions. In experimental models of IC-induced pneumonitis and arthritis, vascular and articular lesions were detected. The hemorrhagic lesions in the lungs were shown to be mediated by leukotriene B4 (LTB4) and nitric oxide (NO). PAF was also involved but only when the release of LTB4 was dependent on PAF as shown in the rat pneumonitis model. In the mouse model, LTB4 release was not dependent on PAF and in this situation PAF was no longer essential for the development of the hemorrhagic lesions. Similar results were observed in the IC-induced arthritis model where the articular cartilage lesions were shown to be mediated by LTB4 and NO but by PAF. In these models TNF was also generated and its release was stimulated by PAF. The role of this cytokine in the development of the lesions is, however not clear. Interesting interactions between these mediators were also observed, such as PAF inducing release of LTB4 and of TNF. Based on our data and on recent literature we proposed a hypothesis to explain the mechanisms involved in the development of tissue injury induced by IC.