Expression of a functional laminin receptor (α6β1, very late activation antigen-6) on human eosinophils

Steve N. Georas, Bradley W. McIntyre, Motohiro Ebisawa, John L. Bednarczyk, Sherry A. Sterbinsky, Robert P. Schleimer, Bruce S. Bochner*

*Corresponding author for this work

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The mechanisms responsible for the accumulation of eosinophils at sites of allergic and other inflammatory reactions are unknown, but recent studies have implicated both eosinophil and endothelial adhesion molecules in this process. However, less well studied have been the adhesive interactions between eosinophils and the subendothelial basement membrane and interstitial connective tissues. To test the hypothesis that eosinophils might interact with extracellular matrix proteins, we analyzed purified human eosinophils for the expression and function of various β1 integrins. Using indirect immunofluorescence and flow cytometry, purified eosinophils from mildly allergic donors were found to consistently express the integrin subunits β1 (CD29), α4 (CD49d, very late activation antigen [VLA]-4α), and α6 (CD49f, VLA-6α). No significant expression of the α1, α2, α3, α5, or β4 subunits was detected. Platelet contamination of the eosinophil preparations was excluded by light microscopy and by the inability to detect expression of platelet glycoproteins αv, CD41b, and CD42b. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of eosinophils confirmed the expression of cell-surface β1, α4, and α6. Furthermore, eosinophils purified from allergic donors were shown to adhere to plate- bound laminin, but not to type 1 or type 4 collagen. Adhesion to laminin was concentration-dependent, required divalent cations, and was completely and specifically inhibited by the anti-α6 monoclonal antibody (MoAb) GoH3 and by the anti-β1 MoAb 33B6. Interestingly, the anti-β1 MoAb 18D3 (which like 33B6 blocks eosinophil binding to VCAM-1) did not inhibit eosinophil adhesion to laminin, suggesting that there are functionally distinct epitopes on the β1 subunit. Eosinophils purified from 4 healthy, nonallergic donors also showed α6-dependent adhesion to laminin, although these cells adhered less well. These studies establish the expression of α6β1 on human eosinophils and document its function as a laminin receptor. Interaction of eosinophil α6β1 with laminin, eg, in basement membranes, may contribute to the localization of these cells at inflammatory sites in vivo.

Original languageEnglish (US)
Pages (from-to)2872-2879
Number of pages8
JournalBlood
Volume82
Issue number9
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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