title: Secretory component is cleaved by neutrophil serine proteinases but its epithelial production is increased by neutrophils through NF-kappa B- and p38 mitogen-activated protein kinase-dependent mechanisms.
abstract: We previously showed that expression of polymeric immunoglobulin receptor (pIgR)/secretory component (SC), the epithelial receptor assuming transport of polymeric IgA in mucosal secretions, is strongly decreased in severe chronic obstructive pulmonary disease. Here, we evaluated in vitro the effects of polymorphonuclear neutrophil (PMN) mediators on pIgR/SC. On polyacrylamide gel electrophoresis analysis, soluble SC was rapidly cleaved by supernatants from phorbol-myristate-acetate-activated PMN, through a serine proteinase activity. Moreover, purified PMN serine proteinases also cleaved SC. Similarly, polymeric IgA was rapidly cleaved in monomers by neutrophil elastase, whereas secretory immunoglobulin A was relatively resistant to neutrophil elastase. Surface pIgR on human bronchial epithelial cells was also cleaved by serine proteinases, as shown by immunofluorescence. In contrast, pIgR/SC production by cultured epithelial cells (quantified by enzyme-linked immunosorbent assay) was significantly increased by supernatants from interleukin-8/formylmethionylleucylphenylalanine-activated PMN (122.6 +/- 17.3 versus 70.9 +/- 9 ng/mg protein, P < 0.01). Upregulation of pIgR/SC production by bronchial epithelial cells was abolished by nuclear factor kappa B- and p38 mitogen-activated protein kinase (MAPK) inhibitors. Moreover, supernatants from interleukin-8/formylmethionylleucylphenylalanine-activated PMN induced the phosphorylation of I kappa B-alpha and p38 MAPK in epithelial cells, independently of serine proteinases. Thus, PMN serine proteinases cleave pIgR/SC, whereas activated PMN induce an increased pIgR/SC expression through epithelial activation of nuclear factor kappa B and p38 MAPK pathways.
authors.affiliation: Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, University of Louvain, Brussels, Belgium.
authors.forename: Charles
authors.initials: C
authors.lastname: Pilette
authors.forename: Youssef
authors.initials: Y
authors.lastname: Ouadrhiri
authors.forename: Françoise
authors.initials: F
authors.lastname: Dimanche
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vaerman
authors.forename: Yves
authors.initials: Y
authors.lastname: Sibille
mesh_terms: D001984:Bronchial Neoplasms; D002462:Cell Membrane / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D020928:Mitogen-Activated Protein Kinases / Q000097:blood*; D009101:Multiple Myeloma / Q000097:blood; D016328:NF-kappa B / Q000097:blood* / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology*; D012635:Secretory Component / Q000097:blood* / Q000235:genetics*; D012697:Serine Endopeptidases / Q000097:blood*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D016328:NF-kappa B; D012635:Secretory Component; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases