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 language | English |
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Pages (from-to) | 222-228 |
Number of pages | 7 |
Journal | Immunology |
Volume | 82 |
Issue number | 2 |
Publication status | Published - Jun 1994 |
Keywords
- VASCULAR ENDOTHELIAL-CELLS
- HUMAN NEUTROPHIL ADHERENCE
- PLASMA FIBRONECTIN
- INTEGRIN RECEPTOR
- IDENTIFICATION
- FAMILY
- ATTACHMENT
- DISTINCT
- BINDING
- HETERODIMERS