Integrin αIIbβ3 Induces the Adhesion and Activation of Mast Cells through Interaction with Fibrinogen

Oki, Toshihiko; Kitaura, Jiro; Eto, Koji; Yang, Lifang; Maeda‐Yamamoto, Mari; Inagaki, Nobuya; Nagai, Hiroichi; Yamanishi, Yoshihiro; Nakajina, Hideaki; Kumagai, Hidetoshi; Kitamura, Toshio

doi:10.4049/jimmunol.176.1.52

Cited by 39 publications

(31 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The roles played by each of three sCD40L receptors in platelet activation remain to be determined. Moreover, the expression of ␣IIb␤3 is not restricted to platelets and their progenitors as was recently shown with hematopoietic progenitors (64) and mast cells (20), which also expressed ␣5␤1 (65). Like platelets, activated mast cells express both integrins ␣5␤1 and ␣IIb␤3, and CD40L (66), and could be activated via ␣5␤1 and ␣IIb␤3 following their interaction with CD40L.…”

Section: Discussionmentioning

confidence: 64%

“…rsCD40L Bound to ␣5␤1-Based on the above results, and because sCD40L also binds to ␣IIb␤3 (10, 11), which is selectively expressed on platelets (18), hematopoietic progenitors (19), and mast cells (20) but not on U937 cells (data not shown), we hypothesized that binding of rsCD40L to U937 cells may also be mediated by other members of the integrin superfamily. We first looked for integrin superfamily members that are expressed on U937, K562, and HEK 293 cells but not on BJAB cells.…”

Section: Resultsmentioning

confidence: 92%

See 1 more Smart Citation

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Léveillé

Bouillon

Wen

et al. 2007

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

It was originally thought that the critical role of the CD40 ligand (CD40L) in normal and inflammatory immune responses was mainly mediated through its interaction with the classic receptor, CD40. However, data from CD40L ؊/؊ and CD40؊/؊ mice suggest that the CD40L-induced inflammatory immune response involves at least one other receptor. This hypothesis is supported by the fact that CD40L stabilizes arterial thrombi through an ␣IIb␤3-dependent mechanism. Here we provide evidence that soluble CD40L (sCD40L) binds to cells of the undifferentiated human monocytic U937 cell line in a CD40-and ␣IIb␤3-independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L monoclonal antibody 5C8, anti-␣5␤1 monoclonal antibody P1D6, and soluble ␣5␤1. The direct binding of sCD40L to purified ␣5␤1 was confirmed in a solid phase binding assay. Binding of sCD40L to ␣5␤1 was modulated by the form of ␣5␤1 expressed on the cell surface as the activation of ␣5␤1 by Mn 2؉ or dithiothreitol resulted in the loss of sCD40L binding. Moreover, sCD40L induced the translocation of ␣5␤1 to the Triton X-100-insoluble fraction of U937 cells, the rapid activation of the MAPK pathways ERK1/2, and interleukin-8 gene expression. The binding of sCD40L to CD40 on BJAB cells, an ␣5␤1-negative B cell line, and the resulting activation of ERK1/2 was not inhibited by soluble ␣5␤1, suggesting that sCD40L can bind concomitantly to both receptors. These results document the existence of novel CD40L-dependent pathways of physiological relevance for cells expressing multiple receptors (CD40, ␣5␤1, and ␣IIb␤3) for CD40L. (2). The expression of CD154 is inducible, and its expression on T cells is triggered primarily by T cell receptor signaling and is regulated by CD28-dependent and independent pathways (3) CD40L is stored in platelets and a subpopulation of T cells and rapidly translocates to the cell membrane following T cell and platelet activation (4, 5). A soluble form of biologically active CD40L trimer (sCD40L) is present in the supernatant of activated T cells (6) and platelets (7) and results from the proteolytic cleavage of the homotrimeric CD40L by a metalloproteinase (7).It was originally thought that CD40L had only one receptor, CD40, which is a type I transmembrane protein that is a member of the TNF receptor superfamily. CD40 is expressed on the surface of many immune and non-immune cells, including B lymphocytes, monocytes/macrophages, and dendritic cells, as well as platelets, epithelial, and endothelial cells (8). Most biological functions of CD40L have been attributed to its direct interaction with CD40. However, studies using CD40L Ϫ/Ϫ and CD40 Ϫ/Ϫ mice have suggested that CD40L may also bind to one or more other receptors (9). In support of this hypothesis, it has been elegantly demonstrated that sCD40L interacts with ␣IIb␤3 (GPIIb/IIIa), an integrin expressed on platelets (10), triggering outside-in signaling and inducing platelet activation and spreading (11). CD40L Ϫ/Ϫ mice exhibit increased bleeding time (12) and reduce...

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 92%

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Léveillé

Bouillon

Wen

et al. 2007

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

show abstract

“…It has been reported that extracellular matrix proteins (i.e. fibronectin, fibrinogen, and collagen) affect degranulation by mast cells in addition to their adhesion, migration, and inflammatory responses by binding a wide array of integrins expressed by mast cells [44][45][46]. OPN-induced migration by FSMC was virtually blocked by Ab against either CD44 or integrin av (Fig.…”

Section: Discussionmentioning

confidence: 92%

Osteopontin is produced by mast cells and affects IgE‐mediated degranulation and migration of mast cells

Nagasaka¹,

Matsue²,

Matsushima³

et al. 2008

Eur J Immunol

View full text Add to dashboard Cite

Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and FceRI aggregation in bone marrowderived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN -/-) and -sufficient (OPN +/+ ) mice without significant differences in yield, purity, granularity, and viability. Using OPN -/-FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin av). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN -/-mice compared with OPN +/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions.

show abstract

“…BMMCs or fetal liver mast cells (FLMCs) were generated and cultured as described. [25][26][27] BM-derived macrophage (BMM⌽), BM-derived myeloid dendritic cells (BMmDCs), and BM-derived plasmacytoid dendritic cells (BMpDCs) were cultured as described. 14 The following mutant mice were used: DAP10 Ϫ/Ϫ , 20 DAP12 Ϫ/Ϫ , 28 FcR␥ Ϫ/Ϫ , 29 and Syk ϩ/Ϫ .…”

Section: Cellsmentioning

confidence: 99%

Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells

Yamanishi

Kitaura

Izawa

et al. 2008

Blood

Self Cite

View full text Add to dashboard Cite

IntroductionIt is widely accepted that mast cells are major effector cells in allergic inflammation through a high-affinity IgE receptor (Fc⑀RI). However, recent advances have delineated the significant roles of mast cells in both innate and adaptive immune responses. [1][2][3][4] To find a novel immune receptor expressed on mast cells, we previously performed a signal sequence trap based on retrovirusmediated expression screening (SST-REX). 5 In this screening, we isolated a cDNA for a novel immune receptor, leukocyte mono-Iglike receptor 1 (LMIR1), 6 using cDNA library of bone marrowderived mast cells (BMMCs). Successively, other members of the LMIR family were cloned by searching for sequences homologous with the Ig-like domain of LMIR1. We and others have demonstrated that LMIR1/CMRF-35-like Ig-like molecule-8 (CLM-8)/ myeloid-associated Ig-like receptor-I (MAIR-I)/CD300a and LMIR2/CLM-4/MAIR-II/dendritic cell-derived Ig-like receptor 1 (DIgR1)/CD300d as well as LMIR3/CLM-1 and LMIR4/CLM-5 were a pair of inhibitory and activating, respectively, receptors with high homology in the Ig-like domain. 6-14 LMIR/CLM forms a family of paired receptors mainly expressed in myeloid cells. [6][7][8][9][10][11][12][13][14] In general, activating receptors do not contain any signaling motifs in the short cytoplasmic tails, but transmit signals by associating with immunoreceptor tyrosine-based activation motif (ITAM) or the related activating motif-bearing molecules via a positively charged residue in the transmembrane domain. [15][16][17][18][19] In the present study, we cloned a cDNA for mouse LMIR5 (mLMIR5)/CLM-7 from a BMMC cDNA library. Analysis of DAP10-, DAP12-, and FcR␥-deficient BMMCs demonstrated the predominant role of DAP12 in the activating functions of mLMIR5.Structural differences in immune receptors in mouse versus human cells sometimes result in differing immunologic responses. For example, human NKG2D associates only with DAP10. On the other hand, mouse NKG2D has 2 splice variants, where the long isoform (NKG2D-L) associates exclusively with DAP10 and the short isoform (NKG2D-S) associates with both DAP10 and DAP12. [20][21][22][23] Interestingly, human LMIR5 (hLMIR5)/CD300b/ immune receptor expressed by myeloid cell-3 (IREM-3), 24 but not mLMIR5, contained a putative tyrosine phosphorylation motif (YXN) in its short cytoplasmic tail. The present results indicated that DAP12 plays a primary role in functions of mLMIR5, while both DAP12 and DAP10 play roles in functions of its human counterpart hLMIR5. Consistent with a recent report by MartinezBarriocanal and Sayos, 24 our results also implicated an unidentified adaptor in the hLMIR5-mediated signaling pathway, which was activated through phosphorylation of the tyrosine in the absence of DAP12. In addition, the experiment using DAP12-deficient and The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is here...

show abstract

Integrin αIIbβ3 Induces the Adhesion and Activation of Mast Cells through Interaction with Fibrinogen

Cited by 39 publications

References 73 publications

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

CD40 Ligand Binds to α5β1 Integrin and Triggers Cell Signaling

Osteopontin is produced by mast cells and affects IgE‐mediated degranulation and migration of mast cells

Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells

Contact Info

Product

Resources

About