Tumor necrosis factor alpha is necessary for granulocyte-macrophage-colony-stimulating-factor-induced eosinophil transendothelial migration.
BACKGROUND
We have previously shown that granulocyte macrophage-colony stimulating factor (GM-CSF) was capable of inducing eosinophil migration across naked filters but not endothelial monolayers. Tumor necrosis factor alpha (TNF-alpha) has been shown to be a key factor in granulocyte adhesion and transendothelial migration.


METHODS
We, therefore, pretreated human umbilical vein endothelial cell (HUVEC) monolayers with TNF-alpha and studied whether TNF-alpha could support GM-CSF-induced eosinophil transendothelial migration.


RESULTS
We found that TNF-alpha supported GM-CSF-induced eosinophil transendothelial migration and that this process was: (1) dependent upon GM-CSF and TNF-alpha dose; (2) time-dependent; (3) not due to TNF-alpha having a chemotactic effect itself; (4) not due to TNF-alpha-induced soluble factor production by endothelium, and (5) inhibitable by actinomycin D. We next studied the specificity of this response. Neutrophils did not migrate across TNF-alpha-pretreated endothelium in response to GM-CSF. TNF-alpha pretreatment of A549 human type-II-like epithelial lung cells (A549) did not support GM-CSF-induced transepithelial migration. Neither interleukin (IL)-1 nor GM-CSF pretreatment of the HUVEC supported GM-CSF-induced transendothelial migration. However, IL-5 induced eosinophil migration through naked filters as well as TNF-alpha-pretreated HUVEC in a manner analogous to GM-CSF. Antibodies to ICAM-1, but not VCAM-1 significantly inhibited this response. Although IL-1 did not support GM-CSF-induced eosinophil transendothelial migration, IL-1 and TNF-alpha induced equivalent expression of ICAM-1 on HUVEC.


CONCLUSIONS
Thus, TNF-alpha-supported eosinophil transendothelial migration in response to GM-CSF (and IL-5) is dependent upon ICAM-1, and is both specific and complex.
Erger
R A
RA
Department of Internal Medicine, VA Medical Center and University of Iowa College of Medicine, Iowa City, USA.
Casale
T B
TB
D019138:Antibodies, Blocking; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003609:Dactinomycin / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D019138:Antibodies, Blocking; D007375:Interleukin-1; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003609:Dactinomycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor