Human skin mast cells express functional β1 integrins that mediate adhesion to extracellular matrix proteins

Michele Columbo, Bruce S. Bochner, Gianni Marone

Research output: Contribution to journalArticle

Abstract

We have evaluated the adhesion of human cutaneous mast cells to several components of the extracellular matrix (plasma fibronectin, laminin, collagen type I and IV) and studied whether these cells express the β1 integrins potentially involved in the adhesion to these proteins. Human skin mast cells (5.1 ± 1.5% pure) spontaneously adhered to fibronectin and laminin (0.1 to 10 μg/ml) immobilized on plastic surfaces (e.g., 14 ± 7.2% and 14 ± 4.4% adhesion at 10 μg/ml, respectively). Similar results were obtained with a 90% pure mast cell preparation. In contrast, cutaneous mast cells did not adhere to collagen type I (1.6 ± 0.5% adhesion) or type IV (1.2 ± 0.8% adhesion). Control adhesion in BSA-coated wells was <5%. Mast cell adhesion to fibronectin was optimal after an incubation period of 60 to 90 min (t( 1/2 ) = 28.2 ± 6.2 min), whereas adhesion to laminin was faster (t( 1/2 ) = 10.1 ± 1.2 min), being nearly optimal after a 15-min incubation period. Human skin mast cell adhesion to fibronectin and laminin was found to be dependent on the presence of divalent cations in the extracellular medium. Dual-color immunofluorescence and flow cytometry were used to evaluate whether human skin mast cells (51.3 ± 3.9% pure) express β1 integrins that may mediate cell adhesion to extracellular matrix proteins. These mast cells were found to express VLA (very late Ag)-3 (75.3 ± 35.6 specific fluorescence intensity) and, to lesser degree, VLA-4 and VLA-5 receptors (8.0 ± 2.5 and 6.9 ± 3.2 specific fluorescence intensity, respectively). In contrast, VLA- 1, VLA-2, and VLA-6 integrins were not expressed significantly. mAb to VLA- 3, VLA-4, and VLA-5 each inhibited by 70% skin mast cell adhesion to fibronectin. mAb to VLA-3 nearly abolished mast cells adhesion to laminin, whereas anti-VLA-4 and anti-VLA-5 were ineffective. Finally, immunosuppressant cyclosporin A (100 nM) and FK-506 (10 nM) significantly inhibited mast cell adhesion to both fibronectin and laminin (p < 0.05). Our data demonstrate that human skin mast cells spontaneously adhere to fibronectin and laminin, and that this adhesion is mediated by VLA-3, VLA-4, and/or VLA-5 integrins on these cells. Interactions between these β1 integrins and extracellular matrix proteins may be involved in perivascular tissue localization of human mast cells in vivo.

Original languageEnglish (US)
Pages (from-to)6058-6064
Number of pages7
JournalJournal of Immunology
Volume154
Issue number11
StatePublished - May 31 1995

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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