title: Eotaxin stimulates eosinophil adhesion to human lung microvascular endothelial cells.
abstract: Effects of the human C-C chemokines eotaxin, MIP-1 alpha, and RANTES on human eosinophil or neutrophil adhesion to human lung microvascular endothelial cells (LMVEC) were investigated. Basal adhesion of unstimulated eosinophils to LMVEC was increased following pretreatment of LMVEC with TNF alpha (10ng/ml) for 6h. Stimulation of eosinophils with eotaxin (30 and 100ng/ml) resulted in increased adhesion to LMVEC pretreated with TNF alpha but not culture medium. Neutrophil adhesion was not increased by eotaxin under similar conditions. Neither MIP-1 alpha (3-100 ng/ml) nor RANTES (3-100 ng/ml) increased eosinophil or neutrophil adhesion to LMVEC pretreated for 6 h with either TNF alpha (10 ng/ml) or culture medium. Monoclonal antibodies (mAb) against eosinophil adhesion molecule VLA-4 (2B4; 30 micrograms/ml) but not CD18 (6.5E; 10 micrograms/ml) inhibited eotaxin-induced eosinophil adhesion to TNF alpha-activated LMVEC. 2B4 in combination with 6.5E reduced adhesion to basal levels. These data show that eotaxin, but not MIP-1 alpha or RANTES, stimulates eosinophil adhesion to LMVEC and that this effect can be abolished by anti-VLA-4 and CD18 mAb in combination. These results suggest that eotaxin may facilitate eosinophil migration from blood vessels in the lung by increasing eosinophil adhesion to endothelial cells.
authors.affiliation: National Heart and Lung Institute, Imperial College of Science Technology and Medicine, London, United Kingdom. a.burke-gaffney@ic.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Burke-Gaffney
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D054413:Chemokine CCL11; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology*; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000166:cytology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; D018821:CD18 Antigens; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing