Eosinophils adhere to vascular cell adhesion molecule-1 via podosomes.

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.

• Authors: Mats W Johansson, Ming H Lye, Steven R Barthel, Allison K Duffy, Douglas S Annis, Deane F Mosher
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 31 Issue 4 Pg. 413-22 (Oct 2004) ISSN: 1044-1549 [Print] United States
• PMID: 15220135 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

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