ADHESION TO FIBRONECTIN PRIMES EOSINOPHILS VIA ALPHA(4)/BETA(1) (VLA-4)

Garry Michael Walsh, O CROMWELL, A B KAY, A J WARDLAW, are anwar

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Abstract

Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 mu g/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha(4) beta(1): (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha(4) beta(1) binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 mu g/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C-4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0 .01). Furthermore, this enhancement was significantly inhibited by the alpha(4) beta(1) mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha(4) beta(1) (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalImmunology
Volume82
Issue number2
Publication statusPublished - Jun 1994

Keywords

  • VASCULAR ENDOTHELIAL-CELLS
  • HUMAN NEUTROPHIL ADHERENCE
  • PLASMA FIBRONECTIN
  • INTEGRIN RECEPTOR
  • IDENTIFICATION
  • FAMILY
  • ATTACHMENT
  • DISTINCT
  • BINDING
  • HETERODIMERS

Cite this

Walsh, G. M., CROMWELL, O., KAY, A. B., WARDLAW, A. J., & anwar , A. (1994). ADHESION TO FIBRONECTIN PRIMES EOSINOPHILS VIA ALPHA(4)/BETA(1) (VLA-4). Immunology, 82(2), 222-228.