Expression and function of the Fas receptor on human blood and tissue eosinophils.
The interaction between activated T cells and eosinophils has been proposed to play an important role in the pathogenesis of allergic diseases. T cell-derived cytokines such as interleukin-5 and granulocyte/macrophage colony-stimulating factor inhibit eosinophil apoptosis and may therefore contribute to the development of tissue and blood eosinophilia in these disorders. Withdrawal of these cytokines leads to eosinophil apoptosis in vitro. In contrast, the mechanisms which actively induce apoptosis in eosinophils are at present not completely understood. In this study, we demonstrate that freshly isolated human eosinophils express mRNA and protein for the Fas receptor. Using anti-Fas monoclonal antibody (mAb), we show that Fas activation accelerates apoptotic eosinophil death in vitro. Moreover, treatment of nasal polyps ex vivo with anti-Fas mAb decreased eosinophilic tissue inflammation. However, we observed that blood as well as tissue eosinophils derived from some eosinophilic donors do not express functional Fas receptors, although Fas protein is normally expressed in these cells. This implies that the susceptibility of the Fas receptor is a matter of regulation in eosinophils as previously observed in other systems. These data suggest that Fas ligand/Fas interactions are involved in the regulation of eosinophil apoptosis and that defects in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases.
Hebestreit
H
H
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Yousefi
S
S
Balatti
I
I
Weber
M
M
Crameri
R
R
Simon
D
D
Hartung
K
K
Schapowal
A
A
Blaser
K
K
Simon
H U
HU
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002469:Cell Separation; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood; D009298:Nasal Polyps / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor