Cell and Tissue Research

, Volume 270, Issue 3, pp 469–474 | Cite as

Pericyte involvement in capillary sprouting during angiogenesis in situ

  • Volker Nehls
  • Kristin Denzer
  • Detlev Drenckhahn


To investigate the participation of microvascular pericytes in the process of capillary sprouting, we examined whole-mount preparations of the rat mesentery by use of a double immunofluorescence approach. Angiogenesis was induced by intraperitoneal injections of either the mast cell-degranulating substance compound 48/80 or tumor cell-conditioned medium. Capillary sprouts were visualized by staining with rhodaminconjugated phalloidin and pericytes were simultaneosly stained by an antibody to the intermediate filament protein desmin. Developing pericytes were negative for the smooth-muscle isoform of α-actin, bbut were clearly reactive for desmin. Pericytes appear to be involved in the carliest stages of capillary sprouting. Pericytes were regularly found lying at and in front of the advancing tips of endothelial sprouts. At many sites pericytes were seen to bridge the gap between the leading edges of opposing endothelial sprouts, which were apparently preparing to merge, suggesting that pericytic processes may serve as guiding structures aiding outgrowth of endothelial cells.

Key words

Pericytes Angiogenesis Capillaries Capillary sprouting Desmin Immunocytochemistry Rat Adenocarcinoma cells, rat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA (1989) An activated form of transforming growth factor β is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci USA 86:4544–4548Google Scholar
  2. Ashton A, DeOliveira F (1966) Nomenclature of pericytes. Intramural and extramural. Br J Ophthalmol 50:119–123Google Scholar
  3. Bär Th, Wolff JR (1972) The formation of capillary basement membranes during internal vascularization of the rat's cerebral cortex. Z Zellforsch 133:231–248Google Scholar
  4. Blood CH, Zetter BR (1990) Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochem Biophys Acta 1032:89–118Google Scholar
  5. Crocker DJ, Murad TM, Geer JC (1970) Role of the pericyte in wound healing. An ultrastructural study. Exp Mol Pathol 13:51–65Google Scholar
  6. Diaz-Flores L, Gutiérrez R, Varela H, Rancel N, Valladares F (1991) Microvascular pericytes: a review of their morphological and functional characteristics. Histol Histopathol 6:269–286Google Scholar
  7. Drenckhahn D, Franz H (1986) Identification of actin, α-actinin, and vinculin-containing plaques at the lateral membrane of epithelial cells. J Cell Biol 102:1843–1852Google Scholar
  8. Drenckhahn D, Frotscher M, Kaiser HW (1984) Concentration of F-actin in synaptic formations of the hippocampus as visualized by staining with fluorescent phalloidin. Brain Res 300:381–384Google Scholar
  9. Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288:551–556Google Scholar
  10. Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447Google Scholar
  11. Fujimoto T, Singer SJ (1987) Immunocytochemical studies of desmin and vimentin in pericapillary cells of chicken. J Histochem Cytochem 35:1105–1115Google Scholar
  12. Herman IM, D'Amore PA (1985) Microvascular pericytes contain muscle and non-muscle actins. J Cell Biol 101:43–52Google Scholar
  13. Joyce NC, DeCamilli P, Boyles J (1984) Pericytes, like vascular smooth muscle cells, are immunocytochemically positive for cyclic GMP-dependent protein kinase. Microvasc Res 28:206–219Google Scholar
  14. Joyce NC, Haire MF, Palade GE (1985) Contractile proteins in pericytes. II. Immunocytochemical evidence for the presence of two isomyosins in graded concentrations. J Cell Biol 100:1387–1395Google Scholar
  15. Nakayasu K (1988) Origin of pericytes in neovascularization of rat cornea. Jpn J Ophthalmol 32:105–112Google Scholar
  16. Nehls V, Drenckhahn D (1991a) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154Google Scholar
  17. Nehls V, Drenckhahn D (1991b) Demonstration of actin filament stress fibers in microvascular endothelial cells in situ. Microvasc Res 42:103–112Google Scholar
  18. Norrby K, Jakobsson A, Sörbo J (1986) Mast cell-mediated angiogenesis: a novel experimental model using the rat mesentery. Virchows Arch [B] 52:195–206Google Scholar
  19. Orlidge A, D'Amore PA (1987) Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J Cell Biol 105:1455–1462Google Scholar
  20. Paku S, Paweletz N (1991) First steps of tumor-related angiogenesis. Lab Invest 65:334–346Google Scholar
  21. Paweletz N, Knierim M (1989) Tumor-related angiogenesis. Crit Rev Oncol/Hematol 9:197–242Google Scholar
  22. Pepper MS, Belin D, Montesano R, Orci L, Vassalli J-D (1990) Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro. J Cell Biol 111:743–755Google Scholar
  23. Rhodin JAG, Fujita H (1989) Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analyses. J Submicrosc Cytol Pathol 21:1–34Google Scholar
  24. Sappino AP, Schürch W, Gabbiani G (1990) Biology of disease. Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63:144–161Google Scholar
  25. Schlingemann RO, Rietveld FJR, Kwaspen F, Kerkhof PCM van de, Waal RMW de, Ruiter DJ (1991) Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. Am J Pathol 138:1335–1347Google Scholar
  26. Sims DE (1986) The pericyte — a review. Tissue Cell 18:153–174Google Scholar
  27. Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A mAb against alpha-smooth muscle actin: A new probe for smooth muscle differentiation. J Cell Biol 103:2787–2796Google Scholar
  28. Skalli O, Pelte M-F, Peclet M-C, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M, Orci L (1989) Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem 37:315–321Google Scholar
  29. Verhoeven D, Buyssens N (1988) Desmin-positive stellate cells associated with angiogenesis in a tumour and non-tumour system. Virchows Arch [B] 54:263–272Google Scholar
  30. Wakui S (1988) Two- and three-dimensional ultrastructural observation of two cell angiogenesis in human granulation tissue. Virch Arch [B] 56:127–139Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Volker Nehls
    • 1
  • Kristin Denzer
    • 1
  • Detlev Drenckhahn
    • 1
  1. 1.Anatomisches Institut der UniversitätWürzburgGermany

Personalised recommendations