Interleukin-4 induces tissue eosinophilia in mice: correlation with its in vitro capacity to stimulate the endothelial cell-dependent selective transmigration of human eosinophils.
Interleukin-4 (IL-4) has been shown to play a crucial role in the pathogenesis of allergic disease. In this study, intraperitoneal administration of IL-4 in mice led to selective accumulation of eosinophils, and intradermal injection induced marked eosinophil infiltration. However, IL-4 had no detectable effect on neutrophil accumulation. Preincubation of mouse IL-4 with the neutralizing mAb 11B11 abolished this peritoneal and dermal eosinophilia. These in vivo data correlate with the in vitro capacity of IL-4 to specifically promote the selective transendothelial migration of eosinophils. Supernatants of antigen-stimulated T cell clones derived from hypersensitized individuals induced significant eosinophil transmigration that was inhibited by the neutralizing mAb 8F12 against human IL-4. These experiments impressively demonstrate a link between specific antigenic recognition and the selective recruitment of eosinophils by the endothelial barrier. Furthermore, data are presented supporting our previous evidence that eosinophils need initial priming to transmigrate across IL-4-activated monolayers. Whereas freshly isolated eosinophils from nonallergic individuals failed to transmigrate, the eosinophils from a group of patients with allergic asthma showed spontaneous layer penetration. These data further support the evidence that eosinophils from allergic patients undergo in vivo priming and are functionally different with respect to their capacity to transmigrate.
Moser
R
R
Department of Medicine, University of Zurich, Switzerland.
Groscurth
P
P
Carballido
J M
JM
Bruijnzeel
P L
PL
Blaser
K
K
Heusser
C H
CH
Fehr
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D001249:Asthma / Q000097:blood; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D004802:Eosinophilia / Q000209:etiology* / Q000503:physiopathology; D004804:Eosinophils / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015847:Interleukin-4