title: Human peripheral blood eosinophils express a functional c-kit receptor for stem cell factor that stimulates very late antigen 4 (VLA-4)-mediated cell adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1).
abstract: We evaluated mature peripheral blood eosinophils for their expression of the surface tyrosine kinase, c-kit, the receptor for the stromal cell-derived cytokine, stem cell factor (SCF). Cytofluorographic analysis revealed that c-kit was expressed on the purified peripheral blood eosinophils from 8 of 8 donors (4 nonatopic and 4 atopic) (mean channel fluorescence intensity 2.0- 3. 6-fold, average 2.8 +/- 0.6-fold, greater than the negative control). The uniform and selective expression of c-kit by eosinophils was confirmed by immunohistochemical analysis of peripheral blood buffy coats. The functional integrity of c-kit was demonstrated by the capacity of 100 ng/ml (5 nM) of recombinant human (rh) SCF to increase eosinophil adhesion to 3, 10, and 30 microg/ml of immobilized FN40, a 40-kD chymotryptic fragment of plasma fibronectin, in 15 min by 7.7 +/- 1.4-, 5.3 +/- 3.3-, and 5.4 +/- 0. 2-fold, respectively, and their adhesion to 0.1, 0.5, and 1.0 microg/ml vascular cell adhesion molecule-1 (VCAM-1), by 12.7 +/- 9. 2-, 3.8 +/- 2.5-, and 1.7 +/- 0.6-fold, respectively. The SCF-stimulated adhesion occurred without concomitant changes in surface integrin expression, thereby indicating an avidity-based mechanism. rhSCF (100 ng/ml, 5 nM) was comparable to rh eotaxin (200 ng/ml, 24 nM) in stimulating adhesion. Cell adhesion to FN40 was completely inhibited with antibodies against the alpha4 and beta1 integrin subunits, revealing that the SCF/c-kit adhesion effect was mediated by a single integrin heterodimer, very late antigen 4 (VLA-4). Thus, SCF represents a newly recognized stromal ligand for the activation of eosinophils for VLA-4-mediated adhesion, which could contribute to the exit of these cells from the blood, their tissue localization, and their prominence in inflammatory lesions.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Yuan
authors.forename: K F
authors.initials: KF
authors.lastname: Austen
authors.forename: D S
authors.initials: DS
authors.lastname: Friend
authors.forename: M
authors.initials: M
authors.lastname: Heidtman
authors.forename: J A
authors.initials: JA
authors.lastname: Boyce
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019010:Vascular Cell Adhesion Molecule-1; D019009:Proto-Oncogene Proteins c-kit