Home LiteratureArticle Details
PMID: 9104821 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Soluble domain 1 of platelet-endothelial cell adhesion molecule (PECAM) is sufficient to block transendothelial migration in vitro and in vivo.

The Journal of experimental medicine ·Vol. 185 ·No. 7 ·1997-04-07 ·Pages 1349-57

Liao F, Ali J, Greene T, Muller WA

Abstract

The inflammatory response involves sequential adhesive interactions between cell adhesion molecules of leukocytes and the endothelium. Unlike the several adhesive steps that precede it, transendothelial migration (diapedesis), the step in which leukocytes migrate between apposed endothelial cells, appears to involve primarily one adhesion molecule, platelet-endothelial cell adhesion molecule (PECAM, CD31). Therefore, we have focused on PECAM as a target for antiinflammatory therapy. We demonstrate that soluble chimeras made of the entire extracellular portion of PECAM, or of only the first immunoglobulin domain of PECAM, fused to the Fc portion of IgG, block diapedesis in vitro and in vivo. Furthermore, the truncated form of the PECAM-IgG chimera does not bind stably to its cellular ligand. This raises the possibility of selective anti-PECAM therapies that would not have the untoward opsonic or cell-activating properties of antibodies directed against PECAM.

MeSH Terms
Cell Adhesion/drug effects Cell Movement/drug effects Endothelium, Vascular/physiology Leukocytes/drug effects Monocytes/physiology Neutrophils/physiology Peptide Fragments/pharmacology,therapeutic use Peritonitis/prevention & control Platelet Endothelial Cell Adhesion Molecule-1/genetics,pharmacology,therapeutic use Recombinant Fusion Proteins/pharmacology,therapeutic use Solubility Venules/physiology
Chemicals
Peptide Fragments Platelet Endothelial Cell Adhesion Molecule-1 Recombinant Fusion Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liao F
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021, USA.
Ali J
Greene T
Muller W A
References (40)
40 references, click to expand
  1. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium.
    J Cell Biol. 1995 Jul;130(2):451-60 PMID: 7542249
  2. Blockade of platelet endothelial cell adhesion molecule-1 protects against myocardial ischemia and reperfusion injury in cats.
    J Immunol. 1996 May 1;156(9):3550-7 PMID: 8617985
  3. Involvement of platelet-endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo.
    Science. 1993 Dec 3;262(5139):1580-2 PMID: 8248808
  4. A heterophilic adhesion mechanism for platelet/endothelial cell adhesion molecule 1 (CD31).
    J Exp Med. 1992 May 1;175(5):1401-4 PMID: 1569405
  5. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo.
    J Exp Med. 1994 Mar 1;179(3):1059-64 PMID: 8113674
  6. Transient intercellular adhesion: the importance of weak protein-protein interactions.
    Trends Biochem Sci. 1994 Sep;19(9):354-8 PMID: 7985226
  7. A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules.
    J Cell Biol. 1990 Jun;110(6):2221-9 PMID: 2190992
  8. A soluble multimeric recombinant CD2 protein identifies CD48 as a low affinity ligand for human CD2: divergence of CD2 ligands during the evolution of humans and mice.
    J Exp Med. 1993 May 1;177(5):1439-50 PMID: 7683037
  9. Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1.
    J Exp Med. 1995 Nov 1;182(5):1337-43 PMID: 7595204
  10. Platelet endothelial cell adhesion molecule-1 (PECAM-1) homophilic adhesion is mediated by immunoglobulin-like domains 1 and 2 and depends on the cytoplasmic domain and the level of surface expression.
    J Biol Chem. 1996 Aug 2;271(31):18561-70 PMID: 8702505
  11. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14.
    J Exp Med. 1994 Jan 1;179(1):269-77 PMID: 7505800
  12. Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo.
    J Exp Med. 1987 Dec 1;166(6):1685-701 PMID: 2445894
  13. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes.
    J Immunol. 1992 Apr 1;148(7):1985-92 PMID: 1372018
  14. Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+T lymphocytes.
    Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6403-7 PMID: 1713678
  15. Murine platelet endothelial cell adhesion molecule (PECAM-1)/CD31 modulates beta 2 integrins on lymphokine-activated killer cells.
    Eur J Immunol. 1993 Oct;23(10):2464-71 PMID: 8405046
  16. Mapping the homotypic binding sites in CD31 and the role of CD31 adhesion in the formation of interendothelial cell contacts.
    J Cell Biol. 1995 Mar;128(6):1229-41 PMID: 7534767
  17. PECAM-1 is required for transendothelial migration of leukocytes.
    J Exp Med. 1993 Aug 1;178(2):449-60 PMID: 8340753
  18. Molecular and functional aspects of PECAM-1/CD31.
    Immunol Today. 1994 Oct;15(10):490-5 PMID: 7945775
  19. Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay.
    J Exp Med. 1992 Sep 1;176(3):819-28 PMID: 1512545
  20. A P-selectin-immunoglobulin G chimera is protective in a rabbit ear model of ischemia-reperfusion.
    Surgery. 1995 Apr;117(4):458-65 PMID: 7536354
  21. 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):245-53 PMID: 1377224
  22. Individually distinct Ig homology domains in PECAM-1 regulate homophilic binding and modulate receptor affinity.
    J Biol Chem. 1996 May 10;271(19):11090-8 PMID: 8626652
  23. Cellular and molecular aspects of PECAM-1.
    Nouv Rev Fr Hematol. 1992;34 Suppl:S9-13 PMID: 1340533
  24. Designing CD4 immunoadhesins for AIDS therapy.
    Nature. 1989 Feb 9;337(6207):525-31 PMID: 2536900
  25. A soluble chimeric form of the L1 glycoprotein stimulates neurite outgrowth.
    Neuron. 1995 Jan;14(1):57-66 PMID: 7826641
  26. Molecular cloning and adhesive properties of murine platelet/endothelial cell adhesion molecule 1.
    Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5569-73 PMID: 8516303
  27. Platelet vitronectin receptor expression differentiates Iraqi-Jewish from Arab patients with Glanzmann thrombasthenia in Israel.
    Blood. 1991 Jan 1;77(1):75-83 PMID: 1702031
  28. Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18).
    J Immunol. 1995 Jan 1;154(1):299-307 PMID: 7995949
  29. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily.
    Science. 1990 Mar 9;247(4947):1219-22 PMID: 1690453
  30. Migration of leukocytes across the vascular intima molecules and mechanisms.
    Trends Cardiovasc Med. 1995 Jan-Feb;5(1):15-20 PMID: 21232233
  31. An anti-platelet-endothelial cell adhesion molecule-1 antibody inhibits leukocyte extravasation from mesenteric microvessels in vivo by blocking the passage through the basement membrane.
    J Exp Med. 1996 Jul 1;184(1):229-39 PMID: 8691137
  32. Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1.
    J Cell Sci. 1996 Feb;109 ( Pt 2):437-45 PMID: 8838667
  33. A human endothelial cell-restricted, externally disposed plasmalemmal protein enriched in intercellular junctions.
    J Exp Med. 1989 Aug 1;170(2):399-414 PMID: 2666561
  34. Adhesion receptors of the immune system.
    Nature. 1990 Aug 2;346(6283):425-34 PMID: 1974032
  35. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera.
    Nature. 1991 Jan 10;349(6305):164-7 PMID: 1986307
  36. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.
    Cell. 1994 Jan 28;76(2):301-14 PMID: 7507411
  37. alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow.
    Cell. 1995 Feb 10;80(3):413-22 PMID: 7532110
  38. Administration of noncytolytic IL-10/Fc in murine models of lipopolysaccharide-induced septic shock and allogeneic islet transplantation.
    J Immunol. 1995 May 15;154(10):5590-600 PMID: 7730658
  39. Leukocyte-endothelial adhesion molecules.
    Blood. 1994 Oct 1;84(7):2068-101 PMID: 7522621
  40. Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural killer cell transendothelial migration and beta 2 integrin activation.
    J Immunol. 1996 Feb 15;156(4):1515-24 PMID: 8568255
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.7.1349
Published
1997-04-07
Pages
1349-57
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196259
Subset
IM
Grants
NHLBI NIH HHS · R01 HL46849 · United States
External Links
PubMed source DOI: 10.1084/jem.185.7.1349 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2