TY - JOUR
T1 - Differential regulation of eosinophil adhesion under conditions of flow in vivo
AU - Sriramarao, P.
AU - Broide, David H.
PY - 1996
Y1 - 1996
N2 - The proinflammatory role of eosinophils in patients with allergic inflammation is now well recognized. However, the molecular mechanisms mediating the sequential events of eosinophil recruitment from the blood stream to sites of allergic inflammation under conditions of shear force have not been clearly established. Using the xenogeneic rabbit model system to study human eosinophil adhesion under conditions of flow in vivo, we have demonstrated that eosinophils like neutrophils roll, adhere, and extravasate across cytokine-stimulated endothelial cells at physiological shear rates in vivo. Eosinophils rolling on venular endothelial cells is mediated by L-selectin and VLA-4. Mediators of cellular activation such as GM-CSF, PAF, or PMA had a differential effect on neutrophil and eosinophil receptor expression and their rolling function. It would thus appear that acting sequentially or in concert a variety of cytokines, including GM-CSF, RANTES, IL-5, and specific cell adhesion molecules (VLA-4/VCAM-1) might play a critical role in the selective sequestration of eosinophils and other proinflammatory leukocytes into the inflamed tissues during episodes of allergic inflammation. Further understanding of the function of these mediators as well as other traffic signals that regulate eosinophil adhesion will help in developing better therapeutic strategies to block the emigration of eosinophils from the blood stream, and also to inhibit the activation of eosinophils once they have reached sites of tissue inflammation.
AB - The proinflammatory role of eosinophils in patients with allergic inflammation is now well recognized. However, the molecular mechanisms mediating the sequential events of eosinophil recruitment from the blood stream to sites of allergic inflammation under conditions of shear force have not been clearly established. Using the xenogeneic rabbit model system to study human eosinophil adhesion under conditions of flow in vivo, we have demonstrated that eosinophils like neutrophils roll, adhere, and extravasate across cytokine-stimulated endothelial cells at physiological shear rates in vivo. Eosinophils rolling on venular endothelial cells is mediated by L-selectin and VLA-4. Mediators of cellular activation such as GM-CSF, PAF, or PMA had a differential effect on neutrophil and eosinophil receptor expression and their rolling function. It would thus appear that acting sequentially or in concert a variety of cytokines, including GM-CSF, RANTES, IL-5, and specific cell adhesion molecules (VLA-4/VCAM-1) might play a critical role in the selective sequestration of eosinophils and other proinflammatory leukocytes into the inflamed tissues during episodes of allergic inflammation. Further understanding of the function of these mediators as well as other traffic signals that regulate eosinophil adhesion will help in developing better therapeutic strategies to block the emigration of eosinophils from the blood stream, and also to inhibit the activation of eosinophils once they have reached sites of tissue inflammation.
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U2 - 10.1111/j.1749-6632.1996.tb32584.x
DO - 10.1111/j.1749-6632.1996.tb32584.x
M3 - Article
C2 - 8906229
AN - SCOPUS:0029812190
SN - 0077-8923
VL - 796
SP - 218
EP - 225
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -