Complement-dependent acceleration of apoptosis in neutrophils by dialyzer membranes

Recently, we have shown that cuprophan (CU) causes receptor modulation by a CS-dependent mechanism, which is activated by neutrophil-derived reactive oxygen intermediates. The objective of our study was to evaluate the contri bution of dialyzer membranes to the induction of apoptosis in human neutrop hils [polymorphonuclear cells (PMNs)]. PMNs harvested from healthy donors w ere incubated with hollow fibers from a biocompatible membrane polysulfone (PS) and a bioincompatible membrane CU, all in the presence of 25% human se rum. After 4, 8, and 12 hours of incubation at 37 degreesC, apoptosis was q uantitated by counting the numbers of cells showing features of apoptosis o n cytospins by light microscopy and also by flow cytometry using propidium iodide nuclear staining. Compared with PMNs incubated with serum alone, cel ls cultured with fibers of PS demonstrated a higher percentage of apoptosis . Fibers from CU dialyzers led to a more pronounced induction of apoptosis in PMNs, which was significantly higher compared with PS. This effect was p artly mediated by heat-sensitive serum products and depended on the presenc e of divalent cations. In contrast to the recently described C5-dependent p athway in PMN receptor modulation by CU, this effect seemed to depend on th e presence of the complement factor C3. In conclusion, our results indicate that besides the well-known accelerated apoptosis of PMNs in uremia, both biocompatible and bioincompatible dialyzer material itself can accelerate a poptosis in human PMNs.