Ethanol impairs intestinal barrier defense by modulation of immunoglobulin A transport.
BACKGROUND
Increased epithelial permeability may contribute to septic complications after alcohol intoxication. Prior ethanol (EtOH) exposure leads to structural and functional effects on cytoskeletal components important in maintaining barrier integrity. The cytoskeleton is also important in the transcellular transport of proteins including the polymeric immunoglobulin receptor (pIgR) mediated transport of immunoglobulin A (IgA) to the luminal surface of mucosal tissues. We (1) investigated the effects of acute EtOH exposure on cell monolayer barrier integrity and IgA transport and (2) assessed the importance of microtubule function on these functions in vitro.


METHODS
Confluent Madin-Darby canine kidney (MDCK) epithelial cells transfected with pIgR cDNA were exposed to 1% or 5% EtOH, and transcytosis of dimeric IgA was measured. Paclitaxel was used to pretreat a subset of MDCK cells. Results. EtOH exposure resulted in a concentration and time dependent decrease in IgA transcytosis. This was associated with physical derangements in the integrity of the cell monolayer. Pretreatment with paclitaxel completely abrogated these effects.


CONCLUSIONS
EtOH causes both physical and immune derangement of epithelial cell barrier function. Decreased secretory IgA at mucosal surfaces may initiate septic complications after EtOH intoxication.
Diebel
Lawrence N
LN
Department of Surgery, Wayne State University, Detroit, Mich 48201 ,USA.
Liberati
David M
DM
Dulchavsky
Scott A
SA
Diglio
Clement A
CA
Brown
William J
WJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D019281:Dimerization; D004285:Dogs; D000431:Ethanol / Q000633:toxicity*; D007070:Immunoglobulin A / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects / Q000502:physiology*
D007070:Immunoglobulin A; D000431:Ethanol