Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1993 Aug 1; 178(2): 449–460.
PMCID: PMC2191108

PECAM-1 is required for transendothelial migration of leukocytes


Platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and electron microscopy reveal that leukocytes blocked in transmigration remain tightly bound to the apical surface of the endothelial cell, precisely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, mediated by the selectin class of adhesion molecules; tight adhesion, mediated by the leukocyte integrins and their endothelial cell counter-receptors; and now transmigration, which, based on these studies, requires PECAM-1.

Full Text

The Full Text of this article is available as a PDF (2.1M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • MARCHESI VT. The site of leucocyte emigration during inflammation. Q J Exp Physiol Cogn Med Sci. 1961 Apr;46:115–118. [PubMed]
  • MARCHESI VT, FLOREY HW. Electron micrographic observations on the emigration of leucocytes. Q J Exp Physiol Cogn Med Sci. 1960 Oct;45:343–348. [PubMed]
  • van Furth R. Current view on the mononuclear phagocyte system. Immunobiology. 1982 Apr;161(3-4):178–185. [PubMed]
  • Lasky LA. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. [PubMed]
  • Stoolman LM. Adhesion molecules controlling lymphocyte migration. Cell. 1989 Mar 24;56(6):907–910. [PubMed]
  • Gallatin M, St John TP, Siegelman M, Reichert R, Butcher EC, Weissman IL. Lymphocyte homing receptors. Cell. 1986 Mar 14;44(5):673–680. [PubMed]
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]
  • Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990 Jul 13;62(1):3–6. [PubMed]
  • Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation. 1990 Oct;50(4):537–544. [PubMed]
  • Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. [PubMed]
  • Harlan JM. Leukocyte-endothelial interactions. Blood. 1985 Mar;65(3):513–525. [PubMed]
  • Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. [PubMed]
  • von Andrian UH, Chambers JD, McEvoy LM, Bargatze RF, Arfors KE, Butcher EC. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. [PMC free article] [PubMed]
  • Smith CW, Kishimoto TK, Abbassi O, Hughes B, Rothlein R, McIntire LV, Butcher E, Anderson DC, Abbass O. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J Clin Invest. 1991 Feb;87(2):609–618. [PMC free article] [PubMed]
  • Newman PJ, Berndt MC, Gorski J, White GC, 2nd, Lyman S, Paddock C, Muller WA. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science. 1990 Mar 9;247(4947):1219–1222. [PubMed]
  • Muller WA, Ratti CM, McDonnell SL, Cohn ZA. A human endothelial cell-restricted, externally disposed plasmalemmal protein enriched in intercellular junctions. J Exp Med. 1989 Aug 1;170(2):399–414. [PMC free article] [PubMed]
  • Ohto H, Maeda H, Shibata Y, Chen RF, Ozaki Y, Higashihara M, Takeuchi A, Tohyama H. A novel leukocyte differentiation antigen: two monoclonal antibodies TM2 and TM3 define a 120-kd molecule present on neutrophils, monocytes, platelets, and activated lymphoblasts. Blood. 1985 Oct;66(4):873–881. [PubMed]
  • Goyert SM, Ferrero EM, Seremetis SV, Winchester RJ, Silver J, Mattison AC. Biochemistry and expression of myelomonocytic antigens. J Immunol. 1986 Dec 15;137(12):3909–3914. [PubMed]
  • Stockinger H, Gadd SJ, 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 Dec 1;145(11):3889–3897. [PubMed]
  • Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. [PMC free article] [PubMed]
  • Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. [PubMed]
  • Muller WA, Weigl SA. Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay. J Exp Med. 1992 Sep 1;176(3):819–828. [PMC free article] [PubMed]
  • Albelda SM, Muller WA, Buck CA, Newman PJ. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. J Cell Biol. 1991 Sep;114(5):1059–1068. [PMC free article] [PubMed]
  • Muller WA, Berman ME, Newman PJ, DeLisser HM, Albelda SM. A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31). J Exp Med. 1992 May 1;175(5):1401–1404. [PMC free article] [PubMed]
  • Muller WA, Gimbrone MA., Jr Plasmalemmal proteins of cultured vascular endothelial cells exhibit apical-basal polarity: analysis by surface-selective iodination. J Cell Biol. 1986 Dec;103(6 Pt 1):2389–2402. [PMC free article] [PubMed]
  • Wright SD. Methods for the study of receptor-mediated phagocytosis. Methods Enzymol. 1986;132:204–221. [PubMed]
  • Phillips DM, Bourinbaiar AS. Mechanism of HIV spread from lymphocytes to epithelia. Virology. 1992 Jan;186(1):261–273. [PubMed]
  • Deuel TF, Senior RM, Huang JS, Griffin GL. Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest. 1982 Apr;69(4):1046–1049. [PMC free article] [PubMed]
  • Albelda SM, Oliver PD, Romer LH, Buck CA. EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol. 1990 Apr;110(4):1227–1237. [PMC free article] [PubMed]
  • Ashman LK, Aylett GW, Cambareri AC, Cole SR. Different epitopes of the CD31 antigen identified by monoclonal antibodies: cell type-specific patterns of expression. Tissue Antigens. 1991 Nov;38(5):199–207. [PubMed]
  • Spertini O, Luscinskas FW, Kansas GS, Munro JM, Griffin JD, Gimbrone MA, Jr, Tedder TF. Leukocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with an inducible endothelial cell ligand to support leukocyte adhesion. J Immunol. 1991 Oct 15;147(8):2565–2573. [PubMed]
  • Spertini O, Luscinskas FW, Gimbrone MA, Jr, Tedder TF. Monocyte attachment to activated human vascular endothelium in vitro is mediated by leukocyte adhesion molecule-1 (L-selectin) under nonstatic conditions. J Exp Med. 1992 Jun 1;175(6):1789–1792. [PMC free article] [PubMed]
  • Ley K, Gaehtgens P, Fennie C, Singer MS, Lasky LA, Rosen SD. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed]
  • Lo SK, Lee S, Ramos RA, Lobb R, Rosa M, Chi-Rosso G, Wright SD. Endothelial-leukocyte adhesion molecule 1 stimulates the adhesive activity of leukocyte integrin CR3 (CD11b/CD18, Mac-1, alpha m beta 2) on human neutrophils. J Exp Med. 1991 Jun 1;173(6):1493–1500. [PMC free article] [PubMed]
  • Detmers PA, Lo SK, Olsen-Egbert E, Walz A, Baggiolini M, Cohn ZA. Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J Exp Med. 1990 Apr 1;171(4):1155–1162. [PMC free article] [PubMed]
  • Tonnesen MG, Anderson DC, Springer TA, Knedler A, Avdi N, Henson PM. Adherence of neutrophils to cultured human microvascular endothelial cells. Stimulation by chemotactic peptides and lipid mediators and dependence upon the Mac-1, LFA-1, p150,95 glycoprotein family. J Clin Invest. 1989 Feb;83(2):637–646. [PMC free article] [PubMed]
  • Arfors KE, Lundberg C, Lindbom L, Lundberg K, Beatty PG, Harlan JM. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987 Jan;69(1):338–340. [PubMed]
  • Smith CW, Rothlein R, Hughes BJ, Mariscalco MM, Rudloff HE, Schmalstieg FC, Anderson DC. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. J Clin Invest. 1988 Nov;82(5):1746–1756. [PMC free article] [PubMed]
  • Hakkert BC, Rentenaar JM, Van Aken WG, Roos D, Van Mourik JA. A three-dimensional model system to study the interactions between human leukocytes and endothelial cells. Eur J Immunol. 1990 Dec;20(12):2775–2781. [PubMed]
  • Tanaka Y, Albelda SM, Horgan KJ, van Seventer GA, Shimizu Y, Newman W, Hallam J, Newman PJ, Buck CA, Shaw S. CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion. J Exp Med. 1992 Jul 1;176(1):245–253. [PMC free article] [PubMed]
  • Carlo JR, Ruddy S, Studer EJ, Conrad DH. Complement receptor binding of C3b-coated cells treated with C3b inactivator, beta 1H globulin and trypsin. J Immunol. 1979 Aug;123(2):523–528. [PubMed]
  • Wright SD, Rao PE, Van Voorhis WC, Craigmyle LS, Iida K, Talle MA, Westberg EF, Goldstein G, Silverstein SC. Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699–5703. [PMC free article] [PubMed]
  • Dana N, Styrt B, Griffin JD, Todd RF, 3rd, Klempner MS, Arnaout MA. Two functional domains in the phagocyte membrane glycoprotein Mo1 identified with monoclonal antibodies. J Immunol. 1986 Nov 15;137(10):3259–3263. [PubMed]
  • Relman D, Tuomanen E, Falkow S, Golenbock DT, Saukkonen K, Wright SD. Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. Cell. 1990 Jun 29;61(7):1375–1382. [PubMed]
  • Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP, Dejana E. A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J Cell Biol. 1992 Sep;118(6):1511–1522. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...