Local thermal injury induces general endothelial cell contraction through p38 MAP kinase activation.
Endothelial cells (ECs) of thin-walled blood vessels form a barrier between blood and tissue. As a response to inflammation, the EC junctions widen and gaps form, resulting in compromised barrier functions. Although the mechanisms behind the establishment of these changes are still incompletely understood, one known reason is actomyosin-dependent actin rearrangement. Here, by using atomic force microscopy and a combination of confocal microscopy methods, we are the first to report that thermal injury induces general venular hyperpermeability and that serum from burned rats induces EC actin rearrangement, contraction, as well as tight-junction damage. Inhibition of the p38 mitogen-activated protein kinase (p38MAPK) largely ameliorates resulting vascular dysfunction by significantly reducing EC stress-fiber formation, contraction, volume changes and tight-junction damage, thereby greatly reducing the appearance of EC gaps. The findings may be of importance for the design of future pharmacotherapies aiming to ease the severe general vascular dysfunction that follows extensive burns.
Department of Pathophysiology, Southern Medical University, Guangzhou, China.
Shuyun
S
Wang
Qiaobing
Q
Huang
Jingxin
J
Guo
Xiaohua
X
Guo
Quanmei
Q
Sun
Ulf T
UT
Brunk
Dong
D
Han
Kesen
K
Zhao
Ming
M
Zhao
D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002056:Burns / Q000097:blood / Q000473:pathology*; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D022502:Stress Fibers / Q000378:metabolism; D019108:Tight Junctions / Q000473:pathology*; D017539:Tunica Intima / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
contraction; endothelial cells; p38 MAPK; permeability; thermal injury