Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1 activation of eosinophil function.
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.
Nagata
M
M
Section of Allergy/Clinical Immunology, Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Sedgwick
J B
JB
Kita
H
H
Busse
W W
WW
D000328:Adult; D000906:Antibodies; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D001249:Asthma / Q000097:blood; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D039441:Integrin alpha4; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D017997:Leukotriene C4 / Q000097:blood; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000097:blood; D012260:Ribonucleases; D013481:Superoxides / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000906:Antibodies; D015703:Antigens, CD; D018821:CD18 Antigens; D011506:Proteins; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D017997:Leukotriene C4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases