TIME-DEPENDENT AND STIMULUS-DEPENDENT SECRETION OF NAP-1 IL-8 BY HUMAN FIBROBLASTS AND ENDOTHELIAL-CELLS/

The neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) has in the past been extensively characterized biochemically as well as funct ionally. Effects of NAP-1/IL-8 on inflammatory cells like neutrophilic granulocytes and lymphocytes, as well as its production by several di fferent cell types, point towards an important role in different infla mmatory processes. Recently, monoclonal antibodies have helped to esta blish immunoassays for detecting the peptide. Using such antibodies, w e have performed in vitro studies on the time- and stimulus-dependent production of IL-8 by endothelial cells as well as fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha) e fficiently induced both focal intracellular expression as well as secr etion of the peptide when tested by immunocytochemistry and enzyme-lin ked immunosorbent assay (ELISA). After stimulation with phorbol myrist ate acetate (PMA) and lipopolysaccharide (LPS), such effects were seen only in endothelial cells, whereas interferon (IFN)-gamma did not ind uce any pronounced effect on either of the cells tested. These studies demonstrated in vitro release of IL-8 by different cells upon specifi c stimulation, thus underlining the significance of the in vivo secret ion of this peptide, as noted in recent studies.