Soluble vascular cell adhesion molecule-1 induces human eosinophil migration.
BACKGROUND
Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated.


METHODS
Peripheral blood eosinophils were purified, and the effect of soluble vascular cell adhesion molecule-1 (sVCAM-1) on eosinophil migration was investigated using in vitro systems.


RESULTS
We found that sVCAM-1 (1 to 10 mug/ml) induced eosinophil chemotaxis, rather than chemokinesis, in a concentration-dependent fashion. In addition, sVCAM-1 induced cell shape change and actin polymerization, which are necessary for cell movement. Manipulations with very late antigen (VLA)-4-neutralizing antibody and signal inhibitors indicated that the sVCAM-1-induced chemotaxis was mediated through ligand-dependent activation of tyrosine kinase Src, p38 mitogen-activated protein kinase (MAPK), and extracellular signal-regulated kinase (ERK) MAPK. Rapid phosphorylation of these signaling molecules was observed using a bead-based multiplex assay.


CONCLUSIONS
Our results raise the possibility of sVCAM-1 in the fluid phase as a significant contributor to the heightened eosinophilic inflammatory response.
Ueki
S
S
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Kihara
J
J
Kato
H
H
Ito
W
W
Takeda
M
M
Kobayashi
Y
Y
Kayaba
H
H
Chihara
J
J
D000199:Actins / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology / Q000502:physiology*
D000199:Actins; D039041:Integrin alpha4beta1; D047428:Protein Kinase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D011494:Protein Kinases