Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes

Am J Respir Cell Mol Biol. 2004 Oct;31(4):413-22. doi: 10.1165/rcmb.2004-0099OC. Epub 2004 Jun 25.

Abstract

Vascular cell adhesion molecule (VCAM)-1 supports specific eosinophil adhesion via alpha4beta1 integrin. We tested the hypothesis that adhesive contacts formed by eosinophils on VCAM-1 are different from focal adhesions formed by adherent fibroblasts. Eosinophils adherent on VCAM-1 formed punctate adhesions that fit the criteria for podosomes, highly dynamic structures found in adherent transformed fibroblasts, osteoclasts, and macrophages. The structures contained beta1 integrin subunit, phosphotyrosine-containing proteins, punctate filamentous actin, and gelsolin, a podosome marker. In contrast, nontransformed fibroblasts on VCAM-1 formed peripheral focal adhesions that were positive for alpha4, beta1, phosphotyrosine, vinculin, talin, and paxillin; negative for gelsolin; and associated with microfilaments. Phorbol myristate acetate or tumor necrosis factor-alpha and interleukin-5 stimulated podosome formation in adherent eosinophils. Because podosomes in tumor cells are associated with extracellular matrix degradation, we analyzed the VCAM-1 layer. VCAM-1 was lost under adherent eosinophils but not under adherent fibroblasts. This loss was inhibited by the metalloproteinase inhibitor ortho-phenanthroline and correlated with expression and podosome localization of a membrane-tethered metalloproteinase, a disintegrin and metalloproteinase domain 8. Podosome-mediated VCAM-1 clearance may be a mechanism to regulate eosinophil arrest and extravasation in allergic conditions such as asthma.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Asthma / metabolism
  • Asthma / pathology*
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Membrane Structures / metabolism
  • Cell Membrane Structures / physiology*
  • Cytoskeletal Proteins / metabolism
  • Disintegrins / metabolism
  • Eosinophils / drug effects
  • Eosinophils / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gelsolin / metabolism
  • Humans
  • Integrin alpha4beta1 / metabolism*
  • Interleukin-5 / pharmacology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Matrix Metalloproteinase 8 / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / metabolism
  • Paxillin
  • Phenanthrolines / pharmacology
  • Phosphoproteins / metabolism
  • Phosphotyrosine / metabolism
  • Rhinitis / metabolism
  • Rhinitis / pathology*
  • Talin / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • Vinculin / metabolism

Substances

  • Actins
  • Cytoskeletal Proteins
  • Disintegrins
  • Gelsolin
  • Integrin alpha4beta1
  • Interleukin-5
  • PXN protein, human
  • Paxillin
  • Phenanthrolines
  • Phosphoproteins
  • Talin
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Vinculin
  • ferroin
  • Phosphotyrosine
  • Matrix Metalloproteinase 8
  • Tetradecanoylphorbol Acetate