The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1

Saalbach, Anja; Kraft, Regine; Herrmann, K.; Haustein, U.‐F.; Anderegg, Ulf

doi:10.1007/s004030050318

Cited by 84 publications

(107 citation statements)

References 13 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Human Thy-1 is involved in the stimulation of MMP-9 release from neutrophils Since human Thy-1 is expressed on TNF-a-activated dermal microvascular EC and dermal fibroblasts [10,23], we studied whether neutrophils might interact with these cells in vivo. Double staining experiments using anti-CD15 antibody to detect neutrophils and an anti-Thy-1-antibody were performed in tissue sections of psoriatic skin lesions.…”

Section: Resultsmentioning

confidence: 99%

“…Human Thy-1 is expressed on activated human dermal microvascular endothelial cells (HDMEC) and constitutively on dermal fibroblasts [23,28]. We demonstrated that Thy-1 Figure 7.…”

Section: Discussionmentioning

confidence: 97%

“…Thy-1 expression was detected in frozen sections of skin biopsies from patients with psoriasis (n = 3) with an anti-Thy-1 antibody [23] and a goat-anti-mouse antibody labeled with alkaline phosphatase. Bound antibodies were visualized colorimetrically using the New Fuchsin substrate system (DAKO, Hamburg, Germany).…”

Section: Immunohistochemistrymentioning

confidence: 99%

See 2 more Smart Citations

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

et al. 2008

Self Cite

View full text Add to dashboard Cite

Neutrophils are the first cells arriving at sites of acute inflammation. On their way from blood to the site of inflammation, neutrophils have to adhere to endothelial cells (EC), to transverse the basement membrane and subsequently to travel through the interstitial matrix. Recently, we have shown that human Thy-1 is an alternate EC receptor for the leukocyte integrin Mac-1 that contributes to leukocyte recruitment to sites of inflammation, providing a new pathway for adhesion and transmigration of neutrophils. Here, we studied the effect of Thy-1-mediated adhesion on neutrophil functions. Binding of neutrophils to recombinant human Thy-1 stimulated the release of MMP-9 from neutrophils, resulting in their enhanced migration through collagen-IV and matrigel. Further, we showed that neutrophil interaction with Thy-1 stimulated secretion of CXCL8 and thus could support the attraction of additional neutrophils to inflammatory sites. Blocking experiments confirmed the pivotal roles of Thy-1 on activated dermal EC or fibroblasts and its counter receptor CD18 on neutrophils for the regulation of MMP-9 and CXCL8 release from neutrophils. Our results support the general concept that the function of 'adhesion molecules' in particular of human Thy-1, may not only be to provide mechanical support but also regulate neutrophil functions.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Human Thy-1 is expressed on activated human dermal microvascular endothelial cells (HDMEC) and constitutively on dermal fibroblasts [23,28]. We demonstrated that Thy-1 Figure 7.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…In humans, Thy-1 is constitutively expressed on fibroblasts, neuronal cells, a subpopulation of blood stem cells, and glomeruli cells [6,8,18,24]. In addition, activated microvascular ECs express Thy-1 [25].…”

Section: Discussionmentioning

confidence: 99%

Thy‐1 (CD90) regulates the extravasation of leukocytes during inflammation

et al. 2011

Self Cite

View full text Add to dashboard Cite

Human Thy-1 (CD90) has been shown to mediate adhesion of inflammatory cells to activated microvascular endothelial cells via interaction with Mac-1 (CD11b/CD18) in vitro. Since there are no data showing the physiological relevance of Thy-1 for the recruitment of inflammatory cells in vivo, different inflammation models were investigated in Thy-1-deficient mice and littermate controls. In thioglycollate-induced peritonitis, the number of neutrophils and monocytes was significantly diminished in Thy-1-deficient mice. During acute lung inflammation, the extravasation of eosinophils and monocytes into the lung was significantly reduced in Thy-1-deficient mice. Moreover, during chronic lung inflammation, the influx of eosinophils and monocytes was also strongly decreased. These effects were independent of Thy-1 expression on T cells, as shown by the transplantation of WT BM into the Thy-1-deficient mice. In spite of the strong Thy-1 expression on T cells in the chimeric mice, the extravasation of the inflammatory cells in these mice was significantly diminished, compared to control mice. Finally, the altered number and composition of infiltrating leukocytes in Thy-1-deficient mice modified the chemokine/cytokine and protease expression at the site of inflammation. In conclusion, Thy-1 is involved in the control of inflammatory cell recruitment and, thus, also in conditioning the inflammatory microenvironment.Key words: Extravasation . Inflammation . Thy-1 Supporting Information available online IntroductionThe recruitment of inflammatory cells to sites of inflammation plays an important role in the pathogenesis of several inflammatory diseases. Leukocyte adhesion to endothelial cells (ECs) follows a multistep process, including the capture of free leukocytes out of the blood stream, rolling, firm adhesion, and transendothelial diapedesis. The importance of several adhesion molecules in this series of events has been described previously [1]. In ICAM-1-deficient mice, neutrophil recruitment was significantly reduced, but it was not completely blocked in a chemical peritonitis model or in a lipopolysaccharide 645(LPS)-induced airway inflammation model, indicating the involvement of additional adhesion molecules [2,3]. Furthermore, leukocyte recruitment in experimental colitis was not affected by blocking ICAM-1 or MadCAM, whereas the blocking of VCAM-1 resulted in a significant attenuation of colitis [4]. Thus, under specific inflammatory conditions, certain adhesion molecules mediate adhesion and transmigration of leukocytes into the perivascular tissue.Recently, human Thy-1 expressed on ECs was identified as an adhesion molecule mediating the binding of neutrophils and monocytes to activated microvascular ECs [5]. Thy-1 is a highly glycosylated GPI-anchored surface protein and a member of the immunoglobulin superfamily [6,7,8]. In humans, Thy-1 is expressed on ECs at sites of inflammation or in tumours whereas ECs do not express Thy-1 in healthy tissue [5,9]. Thy-1 is also expressed on fibroblasts, neurons, and a su...

show abstract

“…Myofibroblasts express ␣-smooth muscle actin (␣-SMA), yet are negative for other smooth muscle markers such as smoothelin and desmin (16,17). These cells are also positive for the marker CD90, which in humans represents a useful fibroblast/ myofibroblast marker because, in humans, it is not expressed by T lymphocytes (35). The subepithelial, pericryptal fibroblastic sheath of the small intestine and colon is composed of intestinal myofibroblasts.…”

mentioning

confidence: 99%

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Saada¹,

Pinchuk²,

Barrera³

et al. 2006

The Journal of Immunology

110

139

View full text Add to dashboard Cite

The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and flow cytometry, we demonstrate that α-smooth muscle actin+, CD90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/86 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

show abstract

The monoclonal antibody AS02 recognizes a protein on human fibroblasts being highly homologous to Thy-1

Cited by 84 publications

References 13 publications

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

Thy‐1 (CD90) regulates the extravasation of leukocytes during inflammation

Subepithelial Myofibroblasts are Novel Nonprofessional APCs in the Human Colonic Mucosa

Contact Info

Product

Resources

About