The basic mechanism of increased microvascular permeability

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1 Chinese Journal of Pathophysiology 2003,19 (4) : [ ] (2003) , (, ) The basic mechanism of increased microvascular permeability ZHAO Ke - sen, HUANG Qiao - bing ( Department of Pathophysiology, First Military Medical University, Guangzhou , China) A Review The increased microvascular permeability appears mainly in venule during inflammation, shock, and burns. Endothelial cells play an important role in venule permeability enhancement. There are two kinds of pathway for macromolecule extravasation. One is paracellular pathway and another is transcellular pathway, which are related to the formation of endothelial gap or transcellular openings seperately. The alter2 ation of intercellular related protein, such as occludin, claudin, zona occludens ( ZO), junctional adhesion molecule (JAM), VE - cadherin, catenin, integrin, etc, and the alteration of endothelial cytoskeleton, such as rearrangement of actin filament, formation of stress fiber and focal adhesion, etc,involve in the pathogenesis of increased microvascular permeability. [] ; ; ; ; [ KEY WORDS] Vascular permeability ;Claudin ; Occludin ; Cadherins ; Stress fiber [] R363 [] A [ ] [ ] [ ] (No ) ; ( G ) ; ( G ) Tel : ; E - mail com,,,,,,, 1,,,, 10-40m (postcapillary venule) ; m, (collecting venule ) 5 - P ( PAF) B 4 (LTB 4 ) TNF LPS -,,, 1. 1 (paracellular pathway) 1961 Majno Palade, 5 - (gap), m, (P ), McDonald, P, ( ),,,,

2 550, (vertical gap) (oblique slits), 1. 2m, (P 1 min),48 % 13,11, 112 (transcellular pathway),,feng 14 nm, nm, - VVOs,, - 3,, VVOs ( ) VVOs, (VEGF) VVOs Michel, VEGF (transcellular opening),,, (vascuolar channel),,, VVOs, (caveolae) (endocytosis) (caveolae), Fig 1 Schema of constructive protein in tight junction. 1 ( 1) (plasmalemmal vesicle), (caveolin) (LDL) Caveolae, (transcytosis) caveolae (molecular ma2 chinery function),- caveolae,src caveolin - 1, caveolin - 1 G ( Gi), caveolae Caveolae,, 2 (gap), -, (tight junc2 tion), ;, ( sealing strand), (oc2 cludin) (claudin) (zona oc2 ( VVOs, vesiculo - vascuolar organelles) cludens, ZO ) ( junction adhesion molecule, JAM) 4,N C (ZO), N C,ZO C ( 1),,, 2. 2 (adherens junction) nm,(cadherin), (tetraspanner protein) -, (VE - cadherin),n N,VE - cadherin (cluster) ; C (catenin), actin (

3 551 2), 20 (anchorage) 3,,N (Arg - Gly - Asp, RGD), RGD, ( FN VN LM ), - ( 3) ( ), Fig 2 The structure of an adherens junction. 2 ( 2) VE - cadherin,, : :,, (gap) ; : -,, ; :,,, (collagen) (laminin,lm) (fibronectin,fn) (vitronectin,vn) nm (extracellular matrix,ecm),, (ad2 hesion of endothelial to basement membrane) (integrin) () ( ), - -,10,8,,, Fig 3 The structure and function of integrins. 3 ( 2) (mechano - sensor) ECM,, G ( Rho Rac ),(),, -, :,;,,, ;,

4 552,,, (tethering property) 3, (cytoskeleton) (isometric contraction),,,,,,, (microtube) (microfilament) (thrombin), (intermediate filament),, 6-8 nm, G Rho, Ca 2 + -, C (actin),,g - actin F - acting - actin,g - actin ( F - actin),,f - actin G - actin, (assembly) (disassembly), 3. 1, Fig 4 Stress fiber. ( PAF TNF ), 4 ( 2),,, 3. 2 ( stress fiber, 4),,, -, ( myosin light (cortical zone), chain, MLC) (myosin, light chain kinase, MLCK) MLC, ATP,, (nonmuscle cell) ( F - actin),, MLCK(ML - 7), (focal MLC contact focal adhesion plaques), ;, PKC Ca PKG (hemidesmosomes) G Rho MAPK (integrin), ECM,,, MLC,,,,

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