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PMID: 8340753 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PECAM-1 is required for transendothelial migration of leukocytes.

The Journal of experimental medicine ·Vol. 178 ·No. 2 ·1993-08-01 ·Pages 449-60

Muller WA, Weigl SA, Deng X, Phillips DM

Abstract

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.

MeSH Terms
Antibodies, Monoclonal/immunology Antigens, Differentiation, Myelomonocytic/physiology Cell Adhesion Cell Adhesion Molecules/physiology Cells, Cultured Chemotaxis, Leukocyte/physiology Endothelium, Vascular/cytology,drug effects,ultrastructure Humans Interleukin-1/pharmacology Microscopy, Electron, Scanning Monocytes/cytology,ultrastructure Neutrophils/cytology,ultrastructure Platelet Endothelial Cell Adhesion Molecule-1 Recombinant Proteins Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Antibodies, Monoclonal Antigens, Differentiation, Myelomonocytic Cell Adhesion Molecules Interleukin-1 Platelet Endothelial Cell Adhesion Molecule-1 Recombinant Proteins Tumor Necrosis Factor-alpha
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Muller W A
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York.
Weigl S A
Deng X
Phillips D M
References (45)
45 references, click to expand
  1. EndoCAM: a novel endothelial cell-cell adhesion molecule.
    J Cell Biol. 1990 Apr;110(4):1227-37 PMID: 2182647
  2. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo.
    Blood. 1987 Jan;69(1):338-40 PMID: 3539230
  3. Selectins: interpreters of cell-specific carbohydrate information during inflammation.
    Science. 1992 Nov 6;258(5084):964-9 PMID: 1439808
  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. Identification of an inducible endothelial-leukocyte adhesion molecule.
    Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238-42 PMID: 2827173
  6. The role of endothelial cells in inflammation.
    Transplantation. 1990 Oct;50(4):537-44 PMID: 2219269
  7. 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):1493-500 PMID: 1709677
  8. Leukocyte adhesion to endothelium in inflammation.
    Cell. 1990 Jul 13;62(1):3-6 PMID: 2194672
  9. Complement receptor binding of C3b-coated cells treated with C3b inactivator, beta 1H globulin and trypsin.
    J Immunol. 1979 Aug;123(2):523-8 PMID: 88474
  10. Electron micrographic observations on the emigration of leucocytes.
    Q J Exp Physiol Cogn Med Sci. 1960 Oct;45:343-8 PMID: 13766495
  11. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins.
    Cell. 1991 May 31;65(5):859-73 PMID: 1710173
  12. 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):873-81 PMID: 2412619
  13. 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):1155-62 PMID: 1969919
  14. Biochemistry and expression of myelomonocytic antigens.
    J Immunol. 1986 Dec 15;137(12):3909-14 PMID: 3465828
  15. Molecular characterization and functional analysis of the leukocyte surface protein CD31.
    J Immunol. 1990 Dec 1;145(11):3889-97 PMID: 1700999
  16. 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):609-18 PMID: 1991844
  17. A novel endothelial-specific membrane protein is a marker of cell-cell contacts.
    J Cell Biol. 1992 Sep;118(6):1511-22 PMID: 1522121
  18. Methods for the study of receptor-mediated phagocytosis.
    Methods Enzymol. 1986;132:204-21 PMID: 3821510
  19. 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):637-46 PMID: 2521491
  20. Leukocyte-endothelial interactions.
    Blood. 1985 Mar;65(3):513-25 PMID: 3918593
  21. The pathogenesis of atherosclerosis--an update.
    N Engl J Med. 1986 Feb 20;314(8):488-500 PMID: 3511384
  22. A three-dimensional model system to study the interactions between human leukocytes and endothelial cells.
    Eur J Immunol. 1990 Dec;20(12):2775-81 PMID: 1980113
  23. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule.
    J Cell Biol. 1991 Sep;114(5):1059-68 PMID: 1874786
  24. 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
  25. 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
  26. The site of leucocyte emigration during inflammation.
    Q J Exp Physiol Cogn Med Sci. 1961 Apr;46:115-8 PMID: 13766496
  27. Chemotaxis of monocytes and neutrophils to platelet-derived growth factor.
    J Clin Invest. 1982 Apr;69(4):1046-9 PMID: 7076844
  28. 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):7538-42 PMID: 1715568
  29. 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):5699-703 PMID: 6225125
  30. 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):2565-73 PMID: 1717567
  31. 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):1789-92 PMID: 1375271
  32. Mechanism of HIV spread from lymphocytes to epithelia.
    Virology. 1992 Jan;186(1):261-73 PMID: 1370128
  33. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily.
    Science. 1990 Mar 9;247(4947):1219-22 PMID: 1690453
  34. Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration.
    J Clin Invest. 1988 Nov;82(5):1746-56 PMID: 2903180
  35. 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):1375-82 PMID: 2364431
  36. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.
    Cell. 1989 Dec 22;59(6):1203-11 PMID: 2688898
  37. Adhesion molecules controlling lymphocyte migration.
    Cell. 1989 Mar 24;56(6):907-10 PMID: 2647304
  38. 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
  39. Adhesion receptors of the immune system.
    Nature. 1990 Aug 2;346(6283):425-34 PMID: 1974032
  40. Two functional domains in the phagocyte membrane glycoprotein Mo1 identified with monoclonal antibodies.
    J Immunol. 1986 Nov 15;137(10):3259-63 PMID: 2430017
  41. 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):2389-402 PMID: 3782302
  42. Different epitopes of the CD31 antigen identified by monoclonal antibodies: cell type-specific patterns of expression.
    Tissue Antigens. 1991 Nov;38(5):199-207 PMID: 1723541
  43. Current view on the mononuclear phagocyte system.
    Immunobiology. 1982 Apr;161(3-4):178-85 PMID: 7047368
  44. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo.
    Blood. 1991 Jun 15;77(12):2553-5 PMID: 2043760
  45. Lymphocyte homing receptors.
    Cell. 1986 Mar 14;44(5):673-80 PMID: 3004743
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.178.2.449
Published
1993-08-01
Pages
449-60
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191108
Subset
IM
Grants
NHLBI NIH HHS · HL-46849 · United States
External Links
PubMed source DOI: 10.1084/jem.178.2.449 PMC Full Text View journal details
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