Proteinase-3 und Neutrophile Elastase als Initiatoren von Entzündungsreaktionen

Neutrophils are an essential component of the innate immune response. Neutrophil elastase-2 (NE) and proteinase-3 (PR3), two functionally related serine proteases of tandemly arranged single copy genes in mammals, are highly abundant in the granules of neutrophil granulocytes. PR3 and NE show very similar enzyme specificities and are believed to exhibit mainly anti-microbial functions. In order to elucidate the biological roles of PR3 and NE we generated PR3/NE double deficient mice. These PR3/NE -/- mice develop no spontaneous phenotype under pathogen-free conditions and show normal neutrophil granulocyte development. However, when the reverse, passive Arthus reaction (RPA) is initiated in the skin of the protease deficient mice, the development of edema and hemorrhage is significantly diminished compared to wildtype (WT) mice. Histological analyses revealed an impaired neutrophil influx to the sites of immune complex deposition. Of high interest, NE single deficient mice developed a normal immune complex induced inflammation in the course of the RPA compared to WT mice. Furthermore, bone marrow derived PR3/NE -/- neutrophils activated by ICs in vitro exhibited significant defects in the production of reactive oxygen species. These findings strongly suggest an additional role for PR3 and NE as triggers of inflammation and neutrophil activation.

Zentrum für Biologische Wissenschaften

Hochschule für Agrar- und Umweltpädagogik
Funktion: Partner