Heparin-binding EGF-like growth factor preserves crypt cell proliferation and decreases bacterial translocation after intestinal ischemia/reperfusion injury.
OBJECTIVE
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a known mitogenic, chemotactic, and cytoprotective growth factor for epithelial cells, was examined to see whether it could protect intestinal barrier function and decrease bacterial translocation (BT) after ischemia/reperfusion (I/R) injury.


METHODS
In vitro, tight junctional integrity of intestinal epithelial cells (IEC-6) cells was evaluated by measuring transepithelial electric resistance (TEER), and monolayer permeability was evaluated by translocation of Escherichia coli C25. In vivo, crypt cell proliferation was assessed by 5-bromodeoxyuridine incorporation with calculation of a proliferative index (PI), and BT was evaluated by culture of mesenteric lymph nodes.


RESULTS
In vitro, anoxia damaged tight junctional integrity and increased permeability of IEC-6 cell monolayers, events that were reversed completely by treatment of the cells with HB-EGF. Twenty-four hours after I/R injury in vivo, crypt cell proliferation index (PI) decreased significantly from 35.6 +/- 4.5 to 17.8 +/- 3.4. Administration of HB-EGF preserved crypt cell activity with PI of 34.9 +/- 4.1, similar to that of normal ileum. None of the normal or sham-operated animals showed BT, whereas BT occurred in 87.5% of I/R-injured rats. In animals exposed to I/R but treated with HB-EGF, BT was decreased significantly to 12.5%.


CONCLUSIONS
HB-EGF preserves proliferation of crypt cells, maintains integrity of epithelial cells, and subsequently decreases enteric BT after I/R injury.
Xia
Guliang
G
Department of Pediatric Surgery, Children's Hospital and The Ohio State University College of Medicine and Public Health Columbus, OH 43205, USA.
Martin
Abigail E
AE
Michalsky
Marc P
MP
Besner
Gail E
GE
D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D066257:Heparin-binding EGF-like Growth Factor; D007082:Ileum / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D019108:Tight Junctions
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor