Neutrophil transepithelial migration: regulation at the apical epithelial surface by Fc-mediated events.
Neutrophil (PMN) transepithelial migration is a major effector of epithelial defense in inflammatory diseases involving mucosal surfaces. However, major receptor-ligand interactions between epithelial cells and PMN remain incompletely characterized. To better define the molecular events involved in PMN interactions with epithelial cells, we produced a monoclonal antibody called g82 that inhibited PMN transepithelial migration in the physiological basolateral-to-apical direction. The g82 antigen localized to the apical surface of human colonic epithelium and was significantly upregulated under inflammatory conditions. Immunoprecipitation revealed two polypeptides of M(r) 207 and 32 kDa. F(ab')(2) fragments from g82 IgG had no effect on transmigration, suggesting Fc dependence. Further experiments confirmed dependence on the PMN Fc receptor CD32A and that the observed effects were secondary to a failure of PMN to detach from the apical epithelial surface. These Fc-mediated events were epitope specific since binding, isotype-matched antibodies did not affect detachment. These results identify a new mechanism for retention of PMN at the apical epithelial surface following transepithelial migration. This pathway may be important in pathogen clearance and mucosal pathophysiology associated with autoimmunity.
Division of Gastrointestinal Pathology, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA. treaves@emory.edu
T A
TA
Reaves
S P
SP
Colgan
P
P
Selvaraj
M M
MM
Pochet
S
S
Walsh
A
A
Nusrat
T W
TW
Liang
J L
JL
Madara
C A
CA
Parkos
D000818:Animals; D002021:Buffers; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000276:immunology; D004847:Epithelial Cells / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011233:Precipitin Tests
D002021:Buffers; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G