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 functionally. Effects of NAP-1/IL-8 on inflammatory cells like neutrophilic granulocytes and lymphocytes, as well as its production by several different cell types, point towards an important role in different inflammatory processes. Recently, monoclonal antibodies have helped to establish immunoassays for detecting the peptide. Using such antibodies, we 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) efficiently induced both focal intracellular expression as well as secretion of the peptide when tested by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). After stimulation with phorbol myristate acetate (PMA) and lipopolysaccharide (LPS), such effects were seen only in endothelial cells, whereas interferon (IFN)-gamma did not induce any pronounced effect on either of the cells tested. These studies demonstrated in vitro release of IL-8 by different cells upon specific stimulation, thus underlining the significance of the in vivo secretion of this peptide, as noted in recent studies.