Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses

Wang, Xiaosong; Kumanogoh, Atsushi; Watanabe, Chie; Shi, Wei; Yoshida, Kanji; Kikutani, Hitoshi

doi:10.1182/blood.v97.11.3498

Cited by 119 publications

(115 citation statements)

References 39 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Sema4D is known to use two types of receptors, plexin-B1 in the nervous system and CD72 in the immune system. plexin-B1 mediates Sema4D-induced axon guidance in the CNS (18), and CD72 mediates Sema4D-dependent modulation of the CD40 pathway in peripheral immune responses (15,30). Despite the expression of CD72 on microglia, the enhancement of iNOS expression was still observed in CD72-deficient microglia.…”

Section: Sema4d Activates Microglia Through Plexin-b1mentioning

confidence: 99%

Roles of Sema4D–Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis

Okuno

Nakatsuji

Moriya

et al. 2009

The Journal of Immunology

Self Cite

102

View full text Add to dashboard Cite

Although semaphorins were originally identified as axonal guidance molecules during neuronal development, it is emerging that several semaphorins play crucial roles in various phases of immune responses. Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors plexin-B1 and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We found that Sema4D promoted inducible NO synthase expression by primary mouse microglia, the effects of which were abolished in plexin-B1–deficient but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein-derived peptides, we observed that the expression of Sema4D and plexin-B1 was induced in infiltrating mononuclear cells and microglia, respectively. Consistent with these expression profiles, when myelin oligodendrocyte glycoprotein-specific T cells derived from wild-type mice were adoptively transferred into plexin-B1–deficient mice or bone marrow chimera mice with plexin-B1–deficient CNS resident cells, the development of EAE was considerably attenuated. Furthermore, blocking Abs against Sema4D significantly inhibited neuroinflammation during EAE development. Collectively, our findings demonstrate the role of Sema4D–plexin-B1 interactions in the activation of microglia and provide their pathologic significance in neuroinflammation.

show abstract

Section: Sema4d Activates Microglia Through Plexin-b1mentioning

confidence: 99%

Roles of Sema4D–Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis

Okuno

Nakatsuji

Moriya

et al. 2009

The Journal of Immunology

Self Cite

102

View full text Add to dashboard Cite

show abstract

“…Although cleavage of sema4D has been observed in T cells (17,18), the protease responsible has not been identified. The observation that sema4D cleavage can occur in washed platelets implies that the protease involved is intrinsic to the platelets and not a plasma protein.…”

Section: Sema4d Is An Integral Protein With a Large N-terminal ␤-Propmentioning

confidence: 99%

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

Zhu¹,

Bergmeier

Wu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

176

221

View full text Add to dashboard Cite

Semaphorin 4D (sema4D; CD100) is an integral membrane protein and the ligand for two receptors, CD72 and plexin-B1. Soluble sema4D has been shown to evoke angiogenic responses from endothelial cells and impair monocyte migration, but the origin of soluble sema4D, particularly at sites of vascular injury, has been unclear. Here we show that platelets express sema4D and both of its receptors and provide evidence that these molecules promote thrombus formation. We also show that the surface expression of sema4D and CD72 increases during platelet activation, followed by the gradual shedding of the sema4D extracellular domain. Shedding is blocked by metalloprotease inhibitors and abolished in mouse platelets that lack the metalloprotease ADAM17 (TACE). Mice that lack sema4D exhibit delayed arterial occlusion after vascular injury in vivo, and their platelets show impaired collagen responses in vitro. In resting platelets, as in B lymphocytes, CD72 is associated with the protein tyrosine phosphatase SHP-1. Platelet activation causes dissociation of the complex, as does the addition of soluble sema4D. These findings suggest a dual role for sema4D in vascular responses to injury. As thrombus formation begins, platelet-associated sema4D can bind to its receptors on nearby platelets, promoting thrombus formation. As thrombus formation continues, sema4D is shed from the platelet surface and becomes available to interact with receptors on endothelial cells and monocytes, as well as continuing to interact with platelets.signaling ͉ thrombosis ͉ metalloprotease ͉ CD72 ͉ plexin-B1 P latelet activation typically begins with the exposure of collagen within a damaged vessel wall or the local generation of thrombin, but the establishment of a stable thrombus requires the recruitment of additional platelets and the development of stable contacts between platelets (1). Platelet activation also results in the release from platelets of molecules that can affect nearby cells, including endothelial cells and leukocytes as well as other platelets. In a continuing search for molecules that might contribute to contact-dependent events during thrombus formation, we screened human platelets for members of the semaphorin family. Although sempahorins are best known as regulators of neurite outgrowth and vascular development, individual family members have been shown to participate in a variety of events. Class IV semaphorin [semaphorin 4D (sema4D; CD100)] is a type I integral membrane protein first reported on T cells where it supports B cell development by binding to CD72 (2-4). However, sema4D receptors are not limited to B cells. Prior work has shown that a soluble sema4D extracellular domain fragment can activate endothelial cells by its other known receptor, plexin-B1. This causes endothelial migration, actin rearrangement, and the formation of tube-like structures in vitro, responses that are relevant for wound healing and angiogenesis (5-11). Soluble sema4D has also been shown to inhibit monocyte (12) and dendritic cell (13) migration. ...

show abstract

“…In addition, certain membrane-bound semaphorins (e.g., Sema4D) are proteolytically released ("shed") in the extracellular space in active form. 14,15 Available data indicate that the control of cell migration by semaphorin signals follows three paradigms, illustrated in Figure 1: (A) membrane-bound semaphorins at the cell surface can mediate localized signals to guide migration; (B) secreted/shed molecules can diffuse in the area of expressing cells, and demarcate it as a "no entry" zone (or instead form a chemotactic gradient) for cell populations expressing the specific receptors; (C) migrating cells may establish autocrine loops of secreted/shed semaphorins, to police their own migration: e.g., it was found that the inactivation of autocrine Sema3A signaling in endothelial cells results in increased directional persistence. 16 What are the molecular pathways underlying the control of cell adhesion and cell migration by semaphorins?…”

Section: Functional Role Of Semaphorins In Cell Adhesion and Cell Migmentioning

confidence: 99%

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

Casazza¹,

Fazzari²,

Tamagnone

2007

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

C ell migration is pivotal in embryo development and in the adult. During development, a wide range of progenitor cells travel over long distances before undergoing terminal differentiation. Moreover, the morphogenesis of epithelial tissues and of the cardio-vascular system involves remodelling compact cell layers and the sprouting of new tubular branches. In the adult, cell migration is essential for the leucocytes involved in immune response. Furthermore, invasive and metastatic cancer cells have the distinctive ability to overcome normal tissue boundaries, travel in and out the blood vessels, and settle down in heterologous tissues. Cell migration normally follows strict guidance cues, either attractive, or inhibitory and repulsive. Semaphorins are a wide family of signals guiding cell migration during development and in the adult. Recent findings have established that semaphorin receptors, the plexins, govern cell migration by regulating integrin-based cell substrate adhesion and actin cytoskeleton dynamics, via specific monomeric GTPases. Plexins furthermore recruit tyrosine kinases in receptor complexes, which allows switching between multiple signalling pathways and functional outcomes. In this article, we will review the functional role of semaphorins in cell migration and the implicated molecular mechanisms controlling cell adhesion.

show abstract

Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses

Cited by 119 publications

References 39 publications

Roles of Sema4D–Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis

Roles of Sema4D–Plexin-B1 Interactions in the Central Nervous System for Pathogenesis of Experimental Autoimmune Encephalomyelitis

Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

Contact Info

Product

Resources

About