Eotaxin induces a sustained reduction in the functional adhesive state of very late antigen 4 for the connecting segment 1 region of fibronectin.
BACKGROUND
Eosinophils that have bound to extracellular matrix proteins, such as the connecting segment 1 (CS-1) region of fibronectin, need to deadhere before undergoing chemotaxis through the extracellular matrix.


OBJECTIVE
We have investigated whether eotaxin can regulate the strength of eosinophil adhesion to the CS-1 region of fibronectin.


METHODS
We have used a micropipette single-cell adhesion assay to determine the force of eosinophil adhesion to the CS-1 region of fibronectin.


RESULTS
Eosinophils bound to CS-1 with high avidity, and this binding could be inhibited with neutralizing antibodies to alpha4 integrins expressed by eosinophils or with neutralizing antibodies to CS-1. Eosinophils incubated in the presence of eotaxin demonstrated a transient increase in the force of eosinophil adhesion to CS-1, which was followed by a more sustained reduction in the force of eosinophil adhesion to CS-1, as assessed in the micropipette single-cell adhesion assay. This decreased binding of eosinophils to CS-1 was not due to alterations in very late antigen 4 (VLA-4) receptor number, as assessed with FACS analysis, or alterations in VLA-4 receptor distribution, as assessed with immunofluorescence microscopy.


CONCLUSIONS
These studies suggest that eotaxin can cause a transient increase followed by a more sustained reduction in the functional force of VLA-4 adhesion to CS-1 and thus promote deadhesion of CS-1 adherent eosinophils in the extracellular matrix.
Sung
K P
KP
Bioengineering and Orthopedics and the Department of Medicine, University of California San Diego, La Jolla, CA 92093-0635, USA.
Yang
L
L
Kim
J
J
Ko
D
D
Stachnick
G
G
Castaneda
D
D
Nayar
J
J
Broide
D H
DH
D015703:Antigens, CD / Q000096:biosynthesis; D002448:Cell Adhesion; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*
D015703:Antigens, CD; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D039441:Integrin alpha4