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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2588.)
© 2006 American Heart Association, Inc.

Brief Reviews

Novel Platelet and Vascular Roles for Immunoreceptor Signaling

Frederick F. Samaha; Mark L. Kahn

From Department of Medicine and Division of Cardiology, University of Pennsylvania, Philadelphia, PA.

Correspondence to Mark Kahn, Department of Medicine and Division of Cardiology, University of Pennsylvania, 952 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104. E-mail markkahn{at}mail.med.upenn.edu; or Frederick Samaha, Division of Cardiology, Philadelphia Veterans Administration Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104. E-mail rick.samaha@va.gov

Series Editor: Lawrence Brass
Platelet Activation and the Formation of the Platelet Plug
ATVB In Focus

Previous Brief Reviews in this Series:

•Tsai H-M. Deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura. 2003;23:388–396.
•Quinn MJ, Byzova TV, Qin J, Topol EJ, Plow EF. Integrin _IIbß₃ and its antagonism. 2003;23:945–952.
•Newman PJ, Newman DK. Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology. 2003;23:953–964.
•Flaumenhaft. Molecular basis of platelet granule secretion. 2003;23:1152–1160.

The immunoreceptor signaling pathway has classically been defined by its role in mediating intracellular signals downstream of immune receptors on circulating cells, but recent studies have revealed new and unexpected roles for this pathway in vascular biology. In platelets the immunoreceptor signaling pathway is coupled to 2 structurally distinct platelet collagen receptors, glycoprotein VI and integrin 2ß1, and is required for the activation of platelets after exposure to vessel wall collagen during plaque rupture. During vascular development immunoreceptor signaling is required for proper formation of the lymphatic system, a role that has revealed the contribution of hematopoietic endothelial progenitors to that process. In conjunction with the identification of new biological roles in vascular cell types, new molecular mechanisms of activating this signaling pathway have been discovered, including activation by integrins and immunoreceptor tyrosine activation motifs (ITAMs) on receptors that do not function as part of the immune response. Here we discuss some of these recent findings and their implications for vascular biology and the treatment of human vascular diseases.

Recent studies have revealed novel and diverse roles for immunoreceptor signaling in vascular biology. In the present review we discuss immunoreceptor signaling downstream of platelet collagen receptors and in hematopoietic cells that contribute to the developing lymphatic vascular system, as well as future clinical and scientific directions of this field.

Key Words: vascular biology • immunoreceptor • ITAM • platelet