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Involvement of Heparanase in Empyema: Implication for Novel Therapeutic Approaches

Moshe Lapidot, Uri Barash, Yaniv Zohar, Yuval Geffen, Inna Naroditsky, Neta Ilan, Lael Anson Best and Israel Vlodavsky

Pleural empyema is an inflammatory condition that progresses from acute to chronic, life-threatening, phase. The incidence of empyema has been increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. Despite continued advances in the management of this condition, morbidity and mortality have essentially remained static over the past decade. Better understanding of the disease and the development of new therapeutic approaches are thus critically needed. Heparanase is an endoglucuronidase that cleaves heparan sulfate chains of proteoglycans. These macromolecules are most abounded in the sub-endothelial and sub-epithelial basement membranes and their cleavage by heparanase leads to disassembly of the extracellular matrix that becomes more susceptible to extravasation and dissemination of metastatic and immune cells. Here, we provide evidence that heparanase expression and activity are markedly increased in empyema and pleural fluids, associating with disease progression. Similarly, heparanase expression is increased in a mouse model of empyema initiated by intranasal inoculation of S. pneumonia. Applying this model we show that transgenic mice over expressing heparanase are more resistant to the infection and survive longer.