Antiadhesive role of apical decay-accelerating factor (CD55) in human neutrophil transmigration across mucosal epithelia.
Neutrophil migration across mucosal epithelium during inflammatory episodes involves the precise orchestration of a number a cell surface molecules and signaling pathways. After successful migration to the apical epithelial surface, apically localized epithelial proteins may serve to retain PMN at the lumenal surface. At present, identification of apical epithelial ligands and their PMN counter-receptors remain elusive. Therefore, to define the existence of apical epithelial cell surface proteins involved in PMN-epithelial interactions, we screened a panel of antibodies directed against epithelial plasma membranes. This strategy identified one antibody (OE-1) that both localized to the apical cell membrane and significantly inhibited PMN transmigration across epithelial monolayers. Microsequence analysis revealed that OE-1 recognized human decay-accelerating factor (DAF, CD55). DAF is a highly glycosylated, 70-80-kD, glycosyl-phosphatidyinositol-linked protein that functions predominantly as an inhibitor of autologous complement lysis. DAF suppression experiments using antisense oligonucleotides or RNA interference revealed that DAF may function as an antiadhesive molecule promoting the release of PMN from the lumenal surface after transmigration. Similarly, peptides corresponding to the antigen recognition domain of OE-1 resulted in accumulation of PMN on the apical epithelial surface. The elucidation of DAF as an apical epithelial ligand for PMN provides a target for novel anti-inflammatory therapies directed at quelling unwanted inflammatory episodes.
Lawrence
Donald W
DW
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck St., Boston, MA 02115, USA.
Bruyninckx
Walter J
WJ
Louis
Nancy A
NA
Lublin
Douglas M
DM
Stahl
Gregory L
GL
Parkos
Charles A
CA
Colgan
Sean P
SP
D000595:Amino Acid Sequence; D001665:Binding Sites; D018958:CD55 Antigens / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000166:cytology; D009504:Neutrophils / Q000502:physiology*
D018958:CD55 Antigens