Biological Activity of Soluble CD100. I. The Extracellular Region of CD100 Is Released from the Surface of T Lymphocytes by Regulated Proteolysis

Elhabazi, Abdellah; Delaire, Stéphanie; Bensussan, Armand; Boumsell, Laurence; Bismuth, Georges

doi:10.4049/jimmunol.166.7.4341

Cited by 130 publications

(134 citation statements)

References 49 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…In some respects, the recruitment and subsequent shedding of sema4D as a bioactive fragment resemble the behavior of CD40L, which is also shed from the surface of activated platelets (32). An earlier study showed that sema4D cleavage in Jurkat cells is inhibited by EDTA and EGTA but failed to detect inhibition by the metalloprotease inhibitor, GM6001 (17). The present studies show that in platelets cleavage is blocked by GM6001 or TAPI-2, and both pharmacologic and genetic evidence points toward ADAM17, either serving as the sema4D sheddase or providing a necessary step before the actual sheddase.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…Because sema4D cleavage occurs in activated T cells (17), we asked whether the loss of platelet sema4D might also reflect cleavage. In an initial experiment, platelets were stimulated with collagen.…”

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

confidence: 99%

See 2 more Smart Citations

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

175

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

Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

See 1 more Smart Citation

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

175

221

View full text Add to dashboard Cite

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

“…Foi inicialmente identificada em linfócitos T ativados (BOUGERET et al, 1992) e posteriormente em outros tipos celulares, tanto humanos quanto murinos. CD100 pode ser encontrada como uma proteína de 150 kDa ligada à membrana ou como uma molécula solúvel de 120 kDa (sCD100), originada por uma clivagem proteolítica (ELHABAZI et al, 2001, BASILE et al, 2007, ZHU et al, 2007.…”

Section: Cd100 Seus Receptores E O Sistema Imuneunclassified

Análise da atividade de CD100 na modulação da ativação de macrófagos e sua infectividade por Leishmania (Leishmania) amazonensis.

Galuppo¹

View full text Add to dashboard Cite

Leishmaniasis is caused by trypanosomatids of the genus Leishmania, which infect mainly macrophages. The disease can have cutaneous, mucocutaneous and visceral forms, and over 350 million people worldwide live at risk areas. The main factors that influence form and severity of the disease are the species of Leishmania and the host immune response. Studies based on infected animal models susceptible and resistant to Leishmania show how the immune system of hosts with different profiles affects the survival of the parasite. Considering the importance of macrophages in Leishmania´s infection and the potential role of CD100 in the modulation of macrophage activation, we postulated that this molecule may affect macrophage infectivity. CD100 is known to reduce migration and expression of inflammatory cytokines in human monocytes and dendritic cells, and is induced in macrophages by inflammatory stimuli. Based on these informations, our objectives are to analyze and compare the expression of CD100 on different types of macrophages from BALB/c and C57BL/6 mice lineages and the effects of this molecule in terms of macrophage activation and infectivity by L. amazonensis. We analyzed the expression of CD100 in resident peritoneal macrophages from both strains of mice and the results suggest that macrophages from BALB/c mice express more CD100 than macrophages from C57BL/6 animals. We have also shown that macrophages from both BALB/c and C57BL/6 mice decrease the expression of CD100 along the infection with Leishmania amazonensis promastigotes. Experiments were also performed to analyze the modulation of soluble CD100 (sCD100) over infection of macrophages from both strains. The results show that macrophages from BALB/c mice pre-treated for 24 hours with sCD100 have augmented infection rates in of 4 hours of incubation. When macrophages remained in contact with the sCD100 before, during and after infection, rates increase after 4 and 24 hours of infection. In macrophages from C57BL/6 mice pre-treated for 24 hours with sCD100 and incubated with sCD100 during the infection rates augment in 4 hours of incubation. When macrophages remained in contact with sCD100 throughout the infection, rates increase after 4 and 24 hours of infection. We can therefore conclude that CD100 is expressed by different macrophage types, that it may be related to modulation of Leishmania´s infection and that the infection itself reduces CD100 expression in macrophages.

show abstract

Biological Activity of Soluble CD100. I. The Extracellular Region of CD100 Is Released from the Surface of T Lymphocytes by Regulated Proteolysis

Cited by 130 publications

References 49 publications

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

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

Análise da atividade de CD100 na modulação da ativação de macrófagos e sua infectividade por Leishmania (Leishmania) amazonensis.

Contact Info

Product

Resources

About