Stimulation of the beta(2) integrin, alpha(M)beta(2), triggers tyrosine phosphorylation and cellular degranulation on human eosinophils.
Activation of human eosinophils by specific extracellular stimuli triggers the cellular degranulation response. Because cellular adhesion is critical for this eosinophil degranulation, we have tested the hypothesis that ligation of the beta(2) integrin, alpha(M)beta(2) (Mac-1, CD11b/CD18), leads to intracellular signaling events that contribute to the eosinophil activation response. Recently, we found that engagement of beta(2) integrin using two different approaches, such as cell adhesion induced by IL-5 or direct ligation of alpha(M)beta(2), triggered tyrosine phosphorylation of Cbl, the product of the c-cbl proto-oncogene, paxillin, a cytoskeletal protein, an unidentified 115-kD protein, and subsequent cellular degranulation. The results of this study indicate that engagement of alpha(M)beta(2) on eosinophils triggers an intracellular signaling cascade leading to cellular degranulation. Tyrosine phosphorylation of Cbl, paxillin, and a 115-kD protein may play important roles in adhesion-dependent cellular functions of eosinophils.
Kato
M
M
Department of Pediatrics, Gunma University School of Medicine, Gunma, Japan.
Kita
H
H
Kimura
H
H
Tachibana
A
A
Motegi
Y
Y
Tokuyama
K
K
Morikawa
A
A
D018821:CD18 Antigens / Q000502:physiology*; D015550:Cell Degranulation; D004804:Eosinophils / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D018821:CD18 Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human