Heparin-binding EGF-like growth factor decreases neutrophil-endothelial cell interactions.
BACKGROUND
Hyperadhesiveness of neutrophils (PMN) to vascular endothelial cells (EC) followed by neutrophil transendothelial migration play important roles in the initiation of ischemia/reperfusion (I/R)-mediated injury. We investigated whether the ability of heparin-binding EGF-like growth factor (HB-EGF) to decrease intestinal injury after intestinal I/R is mediated, in part, by its ability to affect PMN-EC interactions and EC junctional integrity.


METHODS
Human umbilical vein EC monolayers were treated with HB-EGF (100 ng/mL) or phosphate-buffered saline followed by anoxia/reoxygenation (A/R). Simultaneously, labeled human PMN were treated with HB-EGF or phosphate-buffered saline and then co-incubated with EC for determination of PMN-EC adherence and PMN transendothelial migration. EC junctional integrity was also determined.


RESULTS
PMN-EC adhesion increased after exposure of EC to A/R compared to EC exposed to normoxia (87% versus 64% binding, P < 0.05, Wilcoxon rank sum test). A/R-induced PMN-EC hyperadherence was significantly decreased by treatment of PMN with HB-EGF compared to nontreated cells (51% versus 87% binding, P < 0.05). HB-EGF significantly decreased PMN transendothelial migration and also augmented EC tight junctional integrity after A/R.


CONCLUSIONS
HB-EGF significantly reduces A/R-induced PMN-EC adhesion and PMN transendothelial migration and augments junctional integrity in vitro. Thus, HB-EGF acts not only as a potent cytoprotective agent for the intestine, but as an anti-inflammatory agent as well.
Rocourt
Dorothy V
DV
Department of Pediatric Surgery, Children's Hospital, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, USA.
Mehta
Veela B
VB
Wu
Dan
D
Besner
Gail E
GE
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor