Download PDF
Thromb Haemost 2001; 85(01): 160-164
DOI: 10.1055/s-0037-1612919
Review Article
Schattauer GmbH

Lack of In Vivo Function of CD31 in Vascular Thrombosis

B. Vollmar
1   Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
,
R. Schmits
2   Department of internal Medicine, University of Saarland, Homburg/Saar, Germany
,
D. Kunz
1   Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
,
M. D. Menger
1   Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
› Author Affiliations
Further Information

Publication History

Received 06 March 2000

Accepted after resubmission 27 July 2000

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

A murine model of endothelial cell injury-based vascular thrombosis was used to test the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) in blood cell aggregate formation and vessel occlusion in vivo. Photochemically-induced thrombus formation was analyzed in detail using intravital fluorescence microscopy of individual microvessels in cremaster muscle preparations of CD31-deficient and wildtype mice. In venules, epi-illumination induced rapid thrombus formation with first platelet deposition after 0.56 ± 0.11min and complete vessel occlusion within 5.05 ± 0.45 min. In arterioles, thrombus formation was markedly delayed with first platelet deposition after 3.03 ± 0.47 min and complete vessel occlusion within 10.04 ± 1.26 min. Kinetics of thrombus formation in both venules (first platelet deposition: 0.52 ± 0.1 min; vessel occlusion: 5.03 ± 0.52 min) and arterioles (first platelet deposition: 3.06 ± 0.68 min; vessel occlusion: 10.02 ± 1.38 min) of CD31-deficient mice was found almost identical compared with that in wildtype animals. Tail bleeding time was 233 ± 24 s in wildtype and 243 ± 32 s in CD31-deficient mice. Moreover, CD31-deficient and wildtype mice revealed comparable interaction of leukocytes to endothelium. This study shows for the first time in vivo that CD31 is not critically involved in blood cell thrombus formation upon endothelial cell injury.

Keywords

Blood cell aggregation - thrombosis - platelet - CD31 - fluorescence microscopy
 

  • References

  • 1 Albelda SM, Oliver PD, Romer LH, Buck CA. EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol 1990; 110: 1227-37.
    CrossrefPubMedGoogle Scholar
  • 2 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; 175: 1401-4.
    CrossrefPubMedGoogle Scholar
  • 3 Famiglietti J, Sun J, DeLisser HM, Albelda SM. Tyrosine residue in exon 14 of the cytoplasmic domain of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates ligand binding specificity. J Cell Biol 1997; 138: 1425-35.
    CrossrefPubMedGoogle Scholar
  • 4 Hua CT, Gamble JR, Vadas MA, Jackson DE. Recruitment and activation of SHP-1 protein-tyrosine phosphatase by human platelet endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem 1998; 273: 28332-40.
    CrossrefPubMedGoogle Scholar
  • 5 Varon D, Jackson DE, Shenkman B, Dardik R, Tamarin I, Savion N, Newman PJ. Platelet/endothelial cell adhesion molecule-1 serves as a costimulatory agonist receptor that modulates integrin-dependent adhesion and aggregation of human platelets. Blood 1998; 91: 500-7.
    PubMedGoogle Scholar
  • 6 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; 114: 1059-63.
    CrossrefPubMedGoogle Scholar
  • 7 Newman PJ, Hillery CA, Albrecht R, Parise LV, Berndt MC, Mazurov AV, Dunlop LC, Zhang J, Rittenhouse SE. Activation-dependent changes in human platelet PECAM-1: phosphorylation, cytoskeletal association, and surface membrane redistribution. J Cell Biol 1992; 119: 239-46.
    CrossrefPubMedGoogle Scholar
  • 8 Zehnder JL, Hirai K, Shatsky M, McGregor JL, Levitt LJ, Leung LLK. The cel adhesion molecule CD31 is phosphorylated after cell activation. J Biol Chem 1992; 267: 5243-9.
    PubMedGoogle Scholar
  • 9 Rosenblum WI, Murata S, Nelson GH, Werner PK, Ranken R, Harmon RC. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arteries. Am J Pathol 1994; 145: 33-6.
    PubMedGoogle Scholar
  • 10 Rosenblum WI, Nelson GH, Wormley B, Werner P, Wang JM, Shih CC-Y. Role of platelet-endothelial cell adhesion molecule (PECAM-1) in platelet adhesion/aggregation over injured but not denuded endothelium in vivo and ex vivo. Stroke 1996; 27: 709-11.
    CrossrefPubMedGoogle Scholar
  • 11 Wu XW, Lian EC. Binding properties and inhibition of platelet aggregation by a monoclonal antibody to CD31 (PECAM-1). Arterioscler Thromb Vasc Biol 1997; 17: 3154-8
    CrossrefPubMedGoogle Scholar
  • 12 Duncan GS, Andrew DP, Takimoto H, Kaufman SA, Yoshida H, Spellberg J, de la Pompa JL, Elia A, Wakeham A, Karan-Tamir B, Muller WA, Senaldi G, Zukowski MM, Mak TW. Genetic evidence for functional redundancy of platelet/endothelial cell adhesion molecule-1 (PECAM-1): CD31-deficient mice reveal PECAM-1-dependent and PECAM-1-independent functions. J Immunol 1999; 162: 3022-30.
    PubMedGoogle Scholar
  • 13 Baez S. An open cremaster muscle preparation for the study of blood vessels by in vivo microscopy. Microvasc Res 1973; 5: 384-94.
    CrossrefPubMedGoogle Scholar
  • 14 Atkinson PM, Taylor DI, Chetty N. Inhibition of platelet aggregation by ketamine hydrochloride. Thromb Res 1985; 40: 227-34.
    CrossrefPubMedGoogle Scholar
  • 15 Glusa E, Markwardt F. Influence of clonidine-like hypotensive drugs on adrenergic platelet reactions. Biochem Pharmacol 1981; 30: 1359-60.
    CrossrefPubMedGoogle Scholar
  • 16 Raptopoulos D, Weaver BM, Papanastassopoulou M, Staddon GE, Parkinson TJ. The effect of xylazine on plasma thromboxane B2 concentration in sheep. J Vet Pharmacol Ther 1995; 18: 438-41.
    CrossrefPubMedGoogle Scholar
  • 17 Laux V, Seiffge D. Platelet function in the dorsal skin fold chamber of the rat. In Vivo 1993; 7: 45-51.
    PubMedGoogle Scholar
  • 18 Roesken F, Ruecker M, Vollmar B, Boeckel N, Morgenstern E, Menger MD. A new model for quantitative in vivo microscopic analysis of thrombus formation and vascular recanalisation: the ear of the hairless (hr/hr) mouse. Thromb Haemost 1997; 78: 1408-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Newman PJ. The biology of PECAM-1. J Clin Invest 1997; 99: 3-8
    CrossrefPubMedGoogle Scholar
  • 20 Elias III CG, Spellberg JP, Karan-Tamir B, Lin C-H, Wang Y-J, McKenna PJ, Muller WA, Zukowski MM, Andrew DP. Ligation of CD31/PECAM-1 modulates the function of lymphocytes, monocytes and neutrophils. Eur J Immunol 1998; 28: 1948-58.
    CrossrefPubMedGoogle Scholar
  • 21 Jackson DE, Ward CM, Wang RG, Newman PJ. The protein tyrosine phosphatase SHP-2 binds platelet/endothelial cell adhesion molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation: evidence for a mechanistic link between PECAM-mediated and integrin-mediated cellular signaling. J Biol Chem 1997; 272: 6986-93.
    CrossrefPubMedGoogle Scholar
  • 22 Miller FN, Sims DE, Schuske DA, Abney DL. Differentiation of light-dye effects in the microcirculation. Microvasc Res 1992; 44: 166-84.
    CrossrefPubMedGoogle Scholar
  • 23 Lindberg RA, Slaaf DW, Lentsch AB, Miller FN. Involvement of nitric oxide and cyclooxygenase products in photoactivation-induced microvascular occlusion. Microvasc Res 1994; 47: 203-21.
    CrossrefPubMedGoogle Scholar
  • 24 Saniabadi AR, Umemura K, Matsumoto N, Sakuma S, Nakashima M. Vessel wall injury and arterial thrombosis induced by a photochemical reaction. Thromb Haemost 1995; 73: 868-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Hermann KS. Platelet aggregation induced in the hamster check pouch by a photochemical process with excited fluorescein isothiocyanate-dextran. Microvasc Res 1983; 26: 238-49.
    CrossrefPubMedGoogle Scholar
  • 26 Watson BD, Dietrich WD, Busto R, Wachel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 1985; 17: 497-504.
    CrossrefPubMedGoogle Scholar
  • 27 Berman ME, Muller WA. 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; 154: 299-307.
    PubMedGoogle Scholar
  • 28 Piali L, Albelda SM, Baldwin HS, Hammel P, Gisler RH, Imhof BA. Murine platelet endothelial cell adhesion molecule (PECAM-1/CD31) modulates ß2 integrins on lymphokine-activated killer cells. Eur J Immunol 1993; 23: 2464-71.
    CrossrefPubMedGoogle Scholar
  • 29 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 ß1 integrin-mediated adhesion. J Exp Med 1992; 176: 245-53.
    CrossrefPubMedGoogle Scholar
  • 30 Metzelaar MJ, Korteweg J, Sixma JJ, Nieuwenhuis HK. Biochemical characterization of PECAM-1 (CD31 antigen) on human platelets. Thromb Haemost 1991; 66: 700-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Newman PJ. Platelet GPIIb-IIIa: molecular variations and alloantigens. Thromb Haemost 1991; 66: 111-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Burk CD, Newman PJ, Lyman S, Gill J, Coller BS, Poncz M. A deletion in the gene for glycoprotein IIb associated with Glanzmann’s thrombasthenia. J Clin Invest 1991; 87: 270-6.
    CrossrefPubMedGoogle Scholar
  • 33 Kahn ML, Diacovo TG, Bainton DF, Lanza F, Trejo J, Coughlin SR. Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype. Blood 1999; 94: 4112-21.
    PubMedGoogle Scholar
  • 34 Mazurov AV, Vinogradov DV, Kabaeva NV, Antonova GN, Romanov YA, Vlasik TN, Antonov AS, Smirnov VN. A monoclonal antibody, VM64, reacts with a 130kDa glycoprotein common to platelets and endothelial cells: Heterogeneity in antibody binding to human aortic endothelial cells. Thromb Haemost 1991; 66: 494-9.
    Article in Thieme ConnectPubMedGoogle Scholar