IL-8 released constitutively by primary bronchial epithelial cells in culture forms an inactive complex with secretory component

The bronchial epithelium is a source of both alpha and beta chemokines and, uniquely, of secretory component (SC), the extracellular ligand-binding do main of the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and alpha (2)-macroglobulin, bind IL-8. Therefore, we tested the hypot hesis that SC binds IL-8, modifying its activity as a neutrophil chemoattra ctant. Primary bronchial epithelial cells were cultured under conditions to optimize SC synthesis. The chemokines IL-8, epithelial neutrophil-activati ng peptide-78, growth-related oncogene alpha, and RANTES were released cons titutively by epithelial cells from both normal and asthmatic donors and de tected in high m.w. complexes with SC. There were no qualitative difference s in the production of SC-chemokine complexes by epithelial cells from norm al or asthmatic donors, and in all cases this was the only form of chemokin e detected. SC contains 15% N-linked carbohydrate, and complete deglycosyla tion with peptide N-glycosidase F abolished IL-8 binding. In micro-Boyden c hamber assays, no IL-8-dependent neutrophil chemotactic responses to epithe lial culture supernatants could be demonstrated. SC dose-dependently (IC50 similar to0.3 nM) inhibited the neutrophil chemotactic response to rIL-8 (1 0 nM) in micro-Boyden chamber assays and also inhibited IL-8-mediated neutr ophil transendothelial migration. SC inhibited the binding of IL-8 to nonsp ecific binding sites on polycarbonate filters and endothelial cell monolaye rs, and therefore the formation of haptotactic gradients, without effects o n IL-8 binding to specific receptors on neutrophils. The data indicate that in the airways IL-8 may be solubilized and inactivated by binding to SC.