在血液循環的白血球能接受發炎訊號的刺激而進行穿越內皮細胞層(transendothelial migration)的動作。此外，單核球在分化的過程中則會反向穿越內皮細胞層(reverse transendothelial migration)而成為樹突狀細胞。而位於血液與周邊組織間的屏障，是內皮細胞藉由接合蛋白所連接而成，其具有調控白血球穿越的功能。由本實驗室最近的研究顯示，多形核白血球(PMN)穿越內皮細胞層時，會引發毗鄰穿越位置的內皮細胞內鈣離子訊號；更進一步，內皮細胞間的接合蛋白於多形核白血球穿越時，會呈現出重新分佈的現象。因此，本研究主要是想瞭解在有趨化物質(fMLP)濃度梯度的誘導下，多形核白血球在反向穿越內皮細胞層時的現象。本實驗中，人類臍靜脈內皮細胞(HUVECs)是養殖在0.4﹪的膠原凝膠薄層上，將此長滿內皮細胞的膠原凝膠薄層浸泡於fMLP中並組裝至流體室內，依序灌流不含fMLP的緩衝液、含多形核白血球的細胞懸浮液及再次灌流含有fMLP的緩衝液。在此條件下，多形核白血球會首先穿越內皮細胞層到達膠原凝膠薄層，並再反向穿越至內皮細胞層的頂端。多形核白血球整個穿越與反向穿越內皮細胞層的過程，會以相位差顯微鏡進行觀察，並在不同的時間點將試樣固定後，以掃描式電子顯微鏡拍攝記錄。此外，也藉由免疫螢光染色的方式觀察VE-cadherin分子在此過程中的動態變化。於本研究中，我們發現(1)穿越過內皮細胞層的多形核白血球會在內皮細胞底部進行橫向的遷移，並離原始穿越位置有相當遠的距離；(2)多形核白血球也能夠以原始的穿越位置進行反向穿越內皮細胞層；(3)多形核白血球的細胞體取代偽足而首先露於內皮細胞層之上；(4)多形核白血球會於反向穿越內皮細胞層後伸展出其偽足；(5)位於多形核白血球反向穿越位置的內皮細胞接合蛋白(VE-cadherin、PECAM-1)呈現出不連續的分佈；(6) VE-cadherin分子會於多形核白血球反向穿越內皮細胞層時，以側推的方式被推開。綜括本研究之結果，應該可對多形核白血球反向穿越內皮細胞層時的相互關係有更深一層的瞭解。

Leukocytes in the circulating bloodstream undergo transendothelial migration in response to inflammatory stimuli. In addition, complicated trafficking behaviors including reverse transmigration occur in monocytes and dendritic cells as part of their differentiation process. Endothelial cells (ECs), the main barrier between blood and tissue, are connected by intercellular junctions, which presumably control leukocyte transmigration. Recent studies from our laboratory have shown that polymorphonuclear leukocyte (PMN) transmigration is accompanied with endothelial [Ca2+]i signaling that only happens in ECs adjacent to the transmigration site. Moreover, the inter-endothelial junction proteins relocate to allow the passage of PMN. This study is to examine in detail the reverse transmigration process of PMN across a monolayer of cultured ECs in response to a gradient of chemoattractant formly-Met-Leu-Phe (fMLP). Human umbilical vein endothelial cells (HUVECs) were cultured on a thin layer of 0.4﹪collagen gel until confluence. The EC monolayer was immersed in fMLP, mounted on a flow chamber and sequentially perfused with a fresh buffer, a PMN suspension, and an fMLP-containing buffer again. PMNs initially transmigrated across the EC monolayer to the collagen gel and reverse transmigrated to the apical side of the EC monolayer. The entire process of PMN transmigration and reverse transmigration across the EC monolayer was traced under phase contrast optics. Specimens were fixed at various times and processed for examination under a scanning electron microscope. In addition, immunostaining technique was used to observe the dynamic movement of VE-cadherin of interest. We found that (1) transmigrated PMNs usually moved laterally underneath the endothelial monolayer before undergoing reverse transmigration at locations some distances away from their original transmigration sites；(2) The process of PMN reverse transendothelial migration could also occur in the original transmigration site；(3) PMN cell bodies, instead of lamellipodia, emerged at the EC apical surface first；(4) PMNs spread out their pseudopodia after reverse transendothelial migration；(5) both EC junction proteins, VE-cadherin and PECAM-1, showed discontinuities at the PMN reverse transmigration site；(6) VE-cadherin molecules were pushed aside by PMNs undergoing reverse transmigration. Results from this study should shed some light on the understanding of endothelial responses during the reverse transmigration of PMN.

目 錄
中文摘要…………………………………………………………..……1
英文摘要………………………………………………………………..3
致 謝…………………………………………………………………….5
目 錄…………………………………………………………………….6
圖目錄…………………………………………………………………..9
附圖目錄………………………………………………………………11
壹、序言…………………………………………………………….…12
黏著連鎖效應……………………………………………………...12
滾動……………………………………………………………13
活化與穩固黏著………………………………………………14
穿越內皮細胞層………………………………………………16
內皮細胞層下遷移……………………………………………17
內皮細胞接合蛋白與白血球之關係……………………………...18
內皮細胞接合蛋白……………………………………………18
接合蛋白調控白血球之穿越…………………………………21
研究動機………………………………………………………...…23
貳、材料與方法…………………………………………………...….25
一、儀器設備……………………………………………………….25
二、材料…………………………………………………………….26
三、方法…………………………………………………………….31
人類臍靜脈內皮細胞之分離與培養…………………………31
人類臍靜脈內皮細胞之繼代培養……………………………32
蓋玻片之清洗與滅菌…………………………………...…….32
0.4﹪膠原凝膠薄層之製備…………………………………...32
0.4﹪膠原凝膠薄層之內皮細胞……………………………...33
流體室各元件之組裝…………………………………………33
趨化物質濃度梯度之形成……………………………………34
多形核白血球之分離與純化…………………………………35
在相位差顯微鏡系統下觀察多形核白血球反向穿越內皮細胞層………………………………………………………………36
在螢光顯微鏡系統下觀察多形核白血球反向穿越內皮細胞層
…………………………………………………………………37
螢光顯微鏡之樣品觀察………………………………………38
掃描式電子顯微鏡之樣品前處理……………………………39
臨界點乾燥……………………………………………………39
樣品金屬覆膜與保存…………………………………………40
掃描式電子顯微鏡之樣品觀察………………………………40
參、結果………………………………………………………….…..42
一、利用流體室製造趨化物質之濃度梯度……………….…….42
二、利用相位差顯微鏡連續記錄多形核白血球反向穿越內皮細胞
層的動態變化………………………………………………...43
多形核白血球穿越內皮細胞層………………………………43
多形核白血球反向穿越內皮細胞層…………………………43
多形核白血球穿越與反向穿越內皮細胞層之位置選擇……43
多形核白血球穿越與反向穿越內皮細胞層之時間比較……44
多形核白血球反向穿越內皮細胞層之端點變化……………44
三、利用掃描式電子顯微鏡觀察多形核白血球反向穿越內皮細胞
層時的形態構造……………………………………………...44
反向穿越內皮細胞層的多形核白血球之形態構造…………44
已反向穿越內皮細胞層的多形核白血球之形態構造………45
四、利用螢光顯微鏡觀察多形核白血球反向穿越內皮細胞層時接
合蛋白分子的分佈現象…………..…………………………..45
五、利用螢光顯微鏡連續記錄活體之多形核白血球反向穿越內皮
細胞層時的分子反應……………………………………..…..46
肆、討論……………………………………………………….……...47
伍、參考資料………………………………………………………….52
圖………………………………………………………………………..65
附圖………………………………………………………………….…81
縮寫表…………………………………………………………………85
作者簡介………………………………………………………………87

Abbassi, O., Kishimoto, T. K., Mcintire, L. V., Anderson, D. C., Smith, C. W. E-selectin supports neutrophil rolling in vitro under conditions of flow. J. Clin. Invest. 1993, 92:2719-2730
Albelda, S. M., Muller, W. A., Buck, C. A., Newman, P. J. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. J. Cell Biol. 1991, 114:1059-1068
Albelda, S. M., Smith, C. W., Ward, P. A. Adhesion molecules and inflammatory injury. FASEB J. 1994, 8:504-512
Anderson, J. M., VanItallie, C. M. Tight junctions and the molecular basis for regulation of paracellular permeability. Am. J. Physiol. 1995, 269:G467-G475
Arnaout, M. A. Structure and function of the leukocyte adhesion molecule CD11/CD18. Blood 1990, 75:1037-1050
Arnaout, M. A., Lanier, L. L., Faller, D. V. Relative contribution of leukocyte molecules Mol, LFA-1, and p150/95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissue- and stimulus-specific. J. Cell. Physiol. 1988, 137:305-309
Berlin, C., Berg, E. L., Briskin, M. J., Andrew, D. P., Kilshaw, P. J., Holzmann, B., Weissman, I. L., Hamann, A., Butcher, E. C. a 4b7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 1993, 74:185-5
Berman, M. E., Muller, W. A. Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increase binding capacity of leukocyte CR3 (CD11b/CD18). J. Immunol. 1995, 154:299-307
Bevilacqua, M., Nelson, R. M. Selectins. J. Clin. Invest. 1993, 91:379-387
Bevilacqua, M. P., Stengelin, S., Gimbrone, M. A., Seed, B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 1989, 243:1160-1165
Bohnsack, J. F., Zhou, X. N. Divalent cation substitution reveals CD18- and very late antigen-dependent pathways that mediate human neutrophil adherence to fibronectin. J. Immunol. 1992, 149:1340-1347
Bonfanti, R., Furie, B. C., Furie, B., Wagner, D. D. PADGEM (GMP-140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 1989, 73:1109-1112
Buckley, C. D., Doyonnas, R., Newton, J. P., Blystone, S. D., Brown, E. J., Watt, S. M., Simmons, D. L. Identification of avb3 as a heterotypic ligand for CD31/PECAM-1. J. Cell Sci. 1996, 109:437-445
Burns, A. R., Bowden, R. A., Macdonell, S. D., Walker, D. C., Odebunmi, T. O., Donnachie, E. M., Simon, S. I., Entman, M. L., Smith, C. W. Analysis of tight junctions during neutrophil transendothelial migration. J. Cell Sci. 2000, 113:45-57
Burns, A. R., Walker, D. C., Brown, E. S., Thurmon, L. T., Bowden, R. A., Keese, C. R., Simon, S. I., Entman, M. L., Smith, C. W. Neutrophil transendothelial migration is independent of tight junctions and occurs preferentially at tricellular cornors. J. Immunol. 1997, 159:2893-2903
Butcher, E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991, 67:1033-1036
Carlos, T. M., Harlan, J. M. Membrane proteins involved in phagocyte adherence to endothelium. Immuno. Rev. 1990, 114:5-28
Carlos, T. M., Harlan, J. M. Leukocyte-endothelial adhesion molecules. Blood 1994, 84:2068-2101
Caveda, L., Martin, P. I., Navarro, P., Breviario, F., Corada, M., Gulino, D., Lampugnani, M. G., Dejana, E. Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin). J. Clin. Invest. 1996, 98:886-893
Corada, M., Mariotti, M., Thurston, G., Smith, K., Kunkel, R., Brockhaus, M., Lampugnani, M. G., Martin, P. I., Stoppacciaro, A., Ruco, L. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc. Natl. Acad. Sci. USA 1999, 96:9815-9820
Damico, G., Bianchi, G., Bernasconi, S., Bersani, L., Piemonti, L., Sozzani, S., Mantovani, A., Allavena, P. Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells. Blood 1998, 92:207-214
Dangerfield, J., Larbi, K. Y., Huang, M. T., Dewar, A., Nourshargh, S. PECAM-1 (CD31) homophilic interaction up-regulates alpha6beta1 on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane. J. Exp. Med. 2002, 196:1201-1211
Dejana, E. Endothelial cell-to-cell adherences junctions: implications in the control of vascular permeability and angiogenesis. J. Clin. Invest. 1996, 98:1949-1953
Dejana, E., Corada, M., Lampugnani, M. G. Endothelial cell-to-cell junctions. FASEB. J. 1995, 9:910-918
Dejana, E., Zanetti, A., Maschio, A. D. Adhesive proteins at endothelial cell-to-cell junctions and leukocyte extravasation. Haemostasis 1996, 26(S4):210-219
Delisser, H. M., Newman, P. J., Albelda, S. M. Molecular and functional aspects of PECAM-1/CD31. Immunol. Today 1994, 15:490-495
Delisser, H. M., Yan, H. C., Newman, P. J., Muller, W. A., Buck, C. A., Albelda, S. M. Platelet/endothelial cell adhesion molecule-1 (CD31)-mediated cellular aggregation involves cell surface glycosaminoglycan. J. Biol. Chem. 1993, 268:16037-16046
Elices, M. J., Osborn, L., Takada, Y., Crouse, C., Luhowsky, S., Hemler, M., Lobb, R. R. VECAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a side distinct from the VLA-4/fibronectin binding site. Cell 1990, 60:577-584
Fougerolles, A. R., Springer, T. A. Intercellular adhesion molecule 3, a third counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes. J. Exp. Med. 1992, 175:185-190
Furie, M. B., Naprstek, B. L., Silverstein, S. C. Migration of neutrophils across monolayer of cultured microvasular endothelial cells: an in vitro model of leukocyte extravasation. J. Cell. Sci. 1987, 88:161-175
Furie, M. B., Tancinco, M. C. A., Smith, C. W. Monoclonal antibodies to leukocyte integrins CD11a/CD18 and CD11b/CD18 or intercellular adhesion molecule-1 inhibit chemoattractant-stimulated neutrophil transendothelial migration in vitro. Blood 1991, 78:2089-2097
Furuse, M., Hirase, T., Itoh, M Nagafuchi, A., Yonemura, S., Tsukita, S., Tsukita, S. H. Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 1993, 123:1777-1788
Ginsberg, M. H., Du, X., Plow, E. F. Inside-out integrin signaling. Curr. Opin. Cell Biol. 1992, 4:766-771
Gotsch, U., Borges, E., Bosse, R., Böggemeyer, E., Simon, M., Mossmann, H., Vestweber, D. VE-cadherin antibody accelerates neutrophil recruitment in vivo. J. Cell Sci. 1997, 110:583-588
Guan, J. L., Hynes R. O. Lymphocyte cells recognize an alternatively spliced segment of fibronectin via integrin receptor a4b1. Cell 1990, 60:53-61
Gumbiner, B., Lowenkopf, T., Apatira, D. Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc. Natl. Acad. Sci. USA 1991, 88:3460-3464
Hakkert, B. C., Kuijpers, T. W., Leeuwenberg, J. F. M., Mourik, J. A., Ross, D. Nutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, VLA-4. Blood 1991, 78:2721-2726
Hallman, R., Jutilia, M. A., Smith, C. W., Anderson, D. C., Kishimoto, T. K., Butcher, E. C. The peripheral lymph node homing receptor, LECAM-1, is involved in CD18-independent adhesion of human neutrophils to endothelium. Biochem. Biophys. Res. Commun. 1991, 174:236-243
Harlan, J. M., Killen, P. D., Senecal, F. M., Schwartz B. R., Yee, E. K., Taylor, R. F., Beatty, P. G., Price, T. H., Ochs, H. D. The role of neutrophil membrane glycoprotein GP150 in neutrophil adherence to endothelium in vivo. Blood 1985, 66:167-178
Huber, A. R., Kunkel, S. L.,Todd, R. F., Weiss, S. L. Regulation of transendothelial migration by endogenous interleukin-8. Science 1991, 254:99
Hynes, R. O., Integrins: versatility, modulation, and signaling in cell adhesion. Cell 1992, 69:11-25
Jackson, D. E., Ward, C. M., Wang, R., Newman, P. J. The protein-tyrosine phosphatase, SHP-2, binds PECAM-1 and forms a distinct signaling complex during platelet aggregation: evidence for mechanistic link between PECAM-1-and integrin-mediated cellular signaling. J. Biol. Chem. 1997, 272:6986-6993
Johnson, L. C., Aurrand, L. M., Imhof, B. A. The parting of the endothelium: miracle, or simply a junctional affair? J. Cell Sci. 2000, 113:921-933
Kishimoto, T. K., Jutila, M. A., Berg, E. L., Butcher, E. C. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 1989, 245:1238-1241
Kuijpers, T. W., Hakkert, B. C., Hart, M. H., Roos, D. Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8. J. Cell Biol. 1992, 117:565-572
Lampugnani, M. G., Dejana, E. Intercellular junctions: structure, signaling, and functional roles. Curr. Opin. Cell Biol. 1997, 9:674-682
Lampugnani, M. G., Resnati, M., Raiteri, M., Pigott, R., Pisacane, A., Houen, G., Ruco, L. P., Dejana, E. A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J. Cell Biol. 1992, 118:1511-1522
Lo, S. K., Seventer, G. A., Levin, S. M., Wright S. D. Two leukocyte receptors (CD11a/CD18 and CD11b/CD18) mediate transient adhesion to endothelium by binding different ligands. J. Immuno. 1989, 143:3325-3329
Martin, P. I., Lostaglio, S., Schneemann, M., Williams, L., Romano, M., Fruscella, P., Panzeri, C., Stoppacciaro A., Ruco, L., Villa, A. Junctional adhesion molecule, a novel membrane of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J. Cell Biol. 1998, 142:117-127
Piali, L. P., Hammel, P., Uherek, C., Bachmann, R. H., Gisler, R. H., Dunon, D., Imhof, B. A. CD31/PECAM-1 is a ligand for aVb3 integrin involved in adhesion of leukocytes to endothelium. J. Cell Biol. 1995, 130:451-460
Mcever, R. P., Beckstead, J. H., Moore, K. L., Marshall, C. L. Bainton, D. F. GMP-140, a platelet a-granule membrane protein is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J. Clin. Invest. 1989, 84:73-82
Moser, R., Schleiffenbaum, B., Groscurth, P., Fehr, J. Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transmigration neutrophil passage. J. Clin. Invest. 1989, 83:444-455
Muller, W. A., Berman, M. E., Newman, P. J., Delisser, H. M., Albelda, S. M. A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31). J. Exp. Med. 1992, 175:1401-1404
Muller, W. A., Weigl, S. A., Deng, X., Phillips, D. M. PECAM-1 is required for transendothelial migration of leukocytes. J. Exp. Med. 1993, 178:449-460
Newman, P. J. The biology of PECAM-1. J. Clin. Invest. 1997, 99:3-8
Newman, P. J., Bernat, M. C., Gorski, J., White, G. C., Lyman, S., Paddock, C., Muller, W. A. PECAM-1 (CD31) cloning and relation to adhesion molecules of immunoglobulin gene superfamily. Science 1990, 247:1219-1222
Newton, J. P., Buckley, C. D., Jones, E. Y., Simmons, D. L. Residues on both faces of the first immunoglobulin fold contribute to homophilic binding sites of PECAM-1/CD31. J. Biol. Chem. 1997, 272:20555-20563
Ostermann, G., Weber, K. S., Zernecke, A., Schroder, A., Weber, C. JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat. Immunol. 2002, 3:151-158
Picker, L. J., Warnock, R. A., Burns, A. R., Doerschuk, C. M., Berg, E. L., Butcher, E. C. The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140. Cell 1991, 66:921-933
Rowbottom, D. G., Green, K. J. Acute exercise effects on the immune system. Med. Sci. Sports Exerc. 2000, 32: s396-405
Sastry, S. K., Horwitz A. F. Integrin cytoplasmic domains: mediator of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling. Curr. Opin. Cell Biol. 1993, 5:819-831
Schenkel, A. R., Mamdouh, Z., Chen, X., Liebman, R. M., Muller, W. A. CD99 plays a major role in the migration of monocyt60es through endothelial junctions. Nat. Immunol. 2002, 3:143-150
Schmelz, M. F., Franke, W. W. Complexus adherens, a new group of desmoplakin-containing junctions in endothelial cells: the syndesmos connecting retothelial cells in lymph nodes. Eur. J. Cell Bio. 1993, 61:274-289
Shaw, S. K., Bamba, P. S., Perkins, B. N., Luscinskas, F. W. Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium. J. Immunol. 2001, 167:2323-2330
Smith, C. W., Kishimoto, T. K., Abbass, O., Hugness, B., Rothlein, R., Mcintire, L. V., Butcher, E., Anderson, D. C., Abbass, O. Chemotatic factors regulated lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J. Clin. Invest. 1991, 87:609-618
Smith, C. W., Marlin, S. D., Rothlein, R., Toman, C., Anderson, D. A. Cooperative interactions of LFA-1 and Mac-1 with intercellur adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vivo. J. Clin. Invest. 1989, 83:2008-2017
Smyth, S. S., Joneckis, C. C., Parise, L. V. Regulation of vascular integrins. Blood 1993, 81:2827-2843
Spertini, O., Kansas, G. S., Munro, J. M., Gviffin, J. D., Tedder, T. F. Regulation of leukocyte migration by activation of the leukocyte adhesion molecule-1 (LAM-1) selectin. Nature 1991, 349:691-694
Spertini, O., Luscinskas, F. W., Kansas, G. S., Munro, J. M., Griffin, J. D., Gimbrone, M. A. J., Tedder, T. F. Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J. Immunol. 1991, 147:2565-2573
Stevenson, B. R., Siciliano, J. D., Mooseker, M. S., Goodenough, D. A. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J. Cell Biol. 1986, 103:755-766
Stockinger, H., Gadd, S. J., Eher, R., Majdic, O., Schreiber, W., Kasinrerk, W., Strass, B., Schnabl, E., Knapp, W. Molecular characterization and functional analysis of the leukocyte surface protein CD31. J. Immunol. 1990, 145:3889-3897
Su, W. H., Chen, H. I., Huang J. P., Jen, C. J. Endothelial [Ca2＋]i signaling during transmigration of polymorphonuclear leukocytes. Blood 2000, 96:3816-3822
Su, W. H., Chen, H. I., Jen, C. J. Differential movements of VE-cadherin and PECAM-1 during transmigration of polymorphonuclear leukocytes through human umbilical vein endothelim. Blood 2002, 100:3597-603
Tsukita, S., Nagafuchi, A., Yonemura, S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr. Opin. Cell Biol. 1992, 4:834-839
Valiron, O., Chevrier, V., Usson, Y., Breviario, F., Job, D., Dejana, E. Desmoplakin expression and organization at human umbilical vein endothelial cell-to-cell junctions. J. Cell Sci. 1996, 109:2141-2149
Vaporciyan, A. A., Delisser, H. M., Yan, H. C., Mendiguren, I. I., Thom, S. R., Jones, M. L., Ward, P. A., Albelda, S. M. Involvement of platelet-endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo. Science 1993, 262:1580-1582
Vestweber, D., Regulation of endothelial cell contacts during leukocyte extravasation. Curr. Opin. Cell Biol. 2002, 14:587-593
VonAndrian, U. H., Chambers, J. D. Mcevoy L. M., Bargatze, R. F., Arfors, K. E., Butcher, E. C. Two-step model of leukocyte-endothelial interaction in inflammation: distinct roles of LECAM-1 and the leukocyte b2 integrin in vivo. Proc. Natl. Acad. Sci. USA 1991, 88:7538-7542
Walzog, B. Schuppan, D., Heimpel, C., Hafezi, M. A., Gaehtgens, P., Ley, K. The leukocyte integrin Mac-1 (CD11b/CD18) contributes to binding of human granulocytes to collegen. Exp. Cell Res. 1995, 218:28-38
Zimmerman, G. A., Prescsott, S. M., Mcintyre T. M. Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol. Today 1992, 13: 93-100