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. 1995 Nov 1;182(5):1337–1343. doi: 10.1084/jem.182.5.1337

Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1

PMCID: PMC2192210  PMID: 7595204

Abstract

During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.

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Selected References

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  1. 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 Sep;114(5):1059–1068. doi: 10.1083/jcb.114.5.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berg E. L., McEvoy L. M., Berlin C., Bargatze R. F., Butcher E. C. L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature. 1993 Dec 16;366(6456):695–698. doi: 10.1038/366695a0. [DOI] [PubMed] [Google Scholar]
  3. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  4. Berman M. E., Muller W. A. 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. [PubMed] [Google Scholar]
  5. Bogen S., Pak J., Garifallou M., Deng X., Muller W. A. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med. 1994 Mar 1;179(3):1059–1064. doi: 10.1084/jem.179.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeLisser H. M., Chilkotowsky J., Yan H. C., Daise M. L., Buck C. A., Albelda S. M. Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties. J Cell Biol. 1994 Jan;124(1-2):195–203. doi: 10.1083/jcb.124.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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 glycosaminoglycans. J Biol Chem. 1993 Jul 25;268(21):16037–16046. [PubMed] [Google Scholar]
  8. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  9. Frey E. A., Miller D. S., Jahr T. G., Sundan A., Bazil V., Espevik T., Finlay B. B., Wright S. D. Soluble CD14 participates in the response of cells to lipopolysaccharide. J Exp Med. 1992 Dec 1;176(6):1665–1671. doi: 10.1084/jem.176.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedlander D. R., Milev P., Karthikeyan L., Margolis R. K., Margolis R. U., Grumet M. The neuronal chondroitin sulfate proteoglycan neurocan binds to the neural cell adhesion molecules Ng-CAM/L1/NILE and N-CAM, and inhibits neuronal adhesion and neurite outgrowth. J Cell Biol. 1994 May;125(3):669–680. doi: 10.1083/jcb.125.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grumet M., Friedlander D. R., Edelman G. M. Evidence for the binding of Ng-CAM to laminin. Cell Adhes Commun. 1993 Sep;1(2):177–190. doi: 10.3109/15419069309095693. [DOI] [PubMed] [Google Scholar]
  12. Grumet M. Structure, expression, and function of Ng-CAM, a member of the immunoglobulin superfamily involved in neuron-neuron and neuron-glia adhesion. J Neurosci Res. 1992 Jan;31(1):1–13. doi: 10.1002/jnr.490310102. [DOI] [PubMed] [Google Scholar]
  13. Milev P., Friedlander D. R., Sakurai T., Karthikeyan L., Flad M., Margolis R. K., Grumet M., Margolis R. U. Interactions of the chondroitin sulfate proteoglycan phosphacan, the extracellular domain of a receptor-type protein tyrosine phosphatase, with neurons, glia, and neural cell adhesion molecules. J Cell Biol. 1994 Dec;127(6 Pt 1):1703–1715. doi: 10.1083/jcb.127.6.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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 May 1;175(5):1401–1404. doi: 10.1084/jem.175.5.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Muller W. A., Ratti C. M., McDonnell S. L., Cohn Z. A. A human endothelial cell-restricted, externally disposed plasmalemmal protein enriched in intercellular junctions. J Exp Med. 1989 Aug 1;170(2):399–414. doi: 10.1084/jem.170.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muller W. A., Weigl S. A., Deng X., Phillips D. M. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993 Aug 1;178(2):449–460. doi: 10.1084/jem.178.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Muller W. A., Weigl S. A. 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. doi: 10.1084/jem.176.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Newman P. J., Berndt M. C., Gorski J., White G. C., 2nd, Lyman S., Paddock C., Muller W. A. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science. 1990 Mar 9;247(4947):1219–1222. doi: 10.1126/science.1690453. [DOI] [PubMed] [Google Scholar]
  19. Piali L., Albelda S. M., Baldwin H. S., Hammel P., Gisler R. H., Imhof B. A. 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):2464–2471. doi: 10.1002/eji.1830231013. [DOI] [PubMed] [Google Scholar]
  20. Rao Y., Wu X. F., Gariepy J., Rutishauser U., Siu C. H. Identification of a peptide sequence involved in homophilic binding in the neural cell adhesion molecule NCAM. J Cell Biol. 1992 Aug;118(4):937–949. doi: 10.1083/jcb.118.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reyes A. A., Akeson R., Brezina L., Cole G. J. Structural requirements for neural cell adhesion molecule-heparin interaction. Cell Regul. 1990 Jul;1(8):567–576. doi: 10.1091/mbc.1.8.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tanaka Y., Albelda S. M., Horgan K. J., van Seventer G. A., Shimizu Y., Newman W., Hallam J., Newman P. J., Buck C. A., 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. doi: 10.1084/jem.176.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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 Dec 3;262(5139):1580–1582. doi: 10.1126/science.8248808. [DOI] [PubMed] [Google Scholar]
  24. Yan H. C., Pilewski J. M., Zhang Q., DeLisser H. M., Romer L., Albelda S. M. Localization of multiple functional domains on human PECAM-1 (CD31) by monoclonal antibody epitope mapping. Cell Adhes Commun. 1995 Feb;3(1):45–66. doi: 10.3109/15419069509081277. [DOI] [PubMed] [Google Scholar]

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