Biochemical and morphological characterization of vascular and lymphocytic interleukin-4 receptors.
The distribution of the interleukin (IL)-4 receptor in normal human and common marmoset (Callithrix jacchus) tissues was examined by immunofluorescence and flow cytometry using monoclonal antibodies specific for the human IL-4 receptor to gain further insight into IL-4-mediated inflammatory and immunological events. IL-4 receptor positivity was unequivocally demonstrated on lymphocytes, predominantly T cells, and on blood vessels in many tissues. Vascular IL-4 receptor immunofluorescence consisted of a strong smooth muscle cell positivity and weaker positive staining of capillary and venular endothelial cells. Subnanomolar concentrations of IL-4 induced a genistein-sensitive up-regulation of VCAM-1 in vascular cell cultures. Tumor necrosis factor-alpha induced a genistein-resistant up-regulation of VCAM-1. IL-4 strongly induced expression of the IL-4 receptor on splenocytes (T lymphocytes) but not on vascular smooth muscle or endothelial cell cultures. Receptor cross-linking to [125I]IL-4 revealed a 65- to 75-kDa accessory receptor subunit consistent with a recently cloned IL-13 receptor associated with the IL-4 receptor on both vascular endothelial and smooth muscle cells. The demonstration of a vascular distribution pattern for the IL-4 receptor in addition to expression on lymphocytes suggests that vascular functional alterations, transduced through a unique IL-4 receptor complex (the type II IL-4 receptor), may be of importance during immunological and allergic inflammatory events.
Schnyder
B
B
Institute of Toxicology, Swiss Federal Institute of Technology-ETH, Schwerzenbach, Switzerland.
Lugli
S M
SM
Schnyder-Candrian
S
S
Eng
V M
VM
Moser
R
R
Banchereau
J
J
Ryffel
B
B
Car
B D
BD
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis* / Q000737:chemistry / Q000502:physiology*; D002144:Callithrix; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008214:Lymphocytes / Q000737:chemistry*; D009130:Muscle, Smooth / Q000737:chemistry* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000032:analysis* / Q000737:chemistry / Q000502:physiology*; D019948:Receptors, Interleukin-4; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D007529:Isoflavones; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D019010:Vascular Cell Adhesion Molecule-1; D019833:Genistein