Cutting Edge: Evidence for a Signaling Partnership Between Urokinase Receptors (CD87) and L-Selectin (CD62L) in Human Polymorphonuclear Neutrophils

Sitrin, Robert G.; Pan, Pauline M.; Blackwood, R. Alexander; Huang, Junhua; Petty, Howard R.

doi:10.4049/jimmunol.166.8.4822

Cited by 46 publications

(26 citation statements)

References 28 publications

(28 reference statements)

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“…Therefore, it is conceivable that uPAR is modulating either selectin binding or function of the ␣4 integrin in this model. Neutrophil uPAR has recently been shown to associate with L-selectin on the cell surface, although the functional significance of this is not known (40). Because we have shown that Ab blockade of L-selectin on the lymphocyte cell surface had no effect on lymphocyte recruitment to the lung in this model (17), uPARmediated modulation of L-selectin function is an unlikely mechanism for diminished recruitment of uPAR Ϫ/Ϫ lymphoblasts.…”

Section: Resultsmentioning

confidence: 77%

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

Gyetko

Sud

Sonstein

et al. 2001

The Journal of Immunology

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The requirement for urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in T lymphocyte migration is unknown. uPA−/− mice have fewer pulmonary lymphocytes in response to certain infections, but its unknown whether this is due to diminished recruitment. Primed, recipient mice were IT inoculated with Ag. Three days later, fluorescently labeled lymphoblasts from background-matched control wild-type (WT), uPA−/−, or uPAR−/− donor mice were injected i.v., and their recruitment was determined. Approximately twice the number of uPA−/− compared with WT lymphoblasts were recruited to the lungs of WT recipients. This difference was eliminated when uPA−/− and WT lymphoblasts were injected into uPA−/− recipients. Thus, the reduced number of lung lymphocytes in infected uPA−/− mice is not due to reduced recruitment. However, uPAR is critically involved in recruitment. Markedly fewer uPAR−/− compared with WT lymphoblasts were recruited to the lung. These findings suggest that uPAR may be a novel target for immune modulation in T lymphocyte-mediated disorders.

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Section: Resultsmentioning

confidence: 77%

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

Gyetko

Sud

Sonstein

et al. 2001

The Journal of Immunology

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“…Considering our results, we hypothesized that the mitogenic activity of uPA is mediated via integrins adjacent to uPAR. It was reported by Sitrin et al that integrins and uPAR are associated via carbohydrate-lectin interaction and that this physical association is necessary for collaboration (23). Recent studies have shown that integrins can activate the p38 MAPK pathway and that · v integrin, p38 MAPK and uPA are functionally linked in breast cancer cells (14).…”

Section: Discussionmentioning

confidence: 99%

Urokinase-type plasminogen activator induces proliferation in breast cancer cells

Gandhari

Arens²,

Majety³

et al. 2006

Int J Oncol

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Abstract. Urokinase-type plasminogen activator (uPA) is implicated in various pathophysiological processes, including extracellular matrix turnover, cell migration and invasion. Our study aimed to determine the role of uPA in both proliferation and mitogen-activated protein kinase (MAPK) pathway. Hence, we analyzed the effects induced by exogeneous addition of domain-specific uPA antibodies and uPAinteracting molecules on proliferation of uPA-suppressed MDA-MB-231 breast cancer cells. uPA expression was reduced to 53% by stable transfection with an antisense/ vector construct and to 65% by siRNA transfection. Immunocytochemical Ki67 staining and flow cytometry (S-phase) analysis indicated a strong decrease of cellular proliferation activity (35% and 38%, respectively). Exogenous addition of high molecular weight-uPA (HMW-uPA) or incubation with the amino terminal fragment (ATF), which lacks the enzymatic activity of uPA, lead to increased cell proliferation. A strong increase of proliferation was absent when the monoclonal antiuPAR antibody IIIF10 (blocking uPA binding site), soluble uPAR (scavenger effect) and phosphatidyl-inositol-specific phopholipase C (PI-PLC, degrading uPAR) was added prior to the addition of HMW-uPA. In conclusion, HMW-uPA and ATF induce proliferation of breast cancer cells by binding to uPAR. Thereby, integrins situated adjacent to uPAR carry the signals into the cell, thus stimulating proliferation that is mediated via the MAPK pathway.

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“…However, uPAR can form a complex with ␤ 1 or ␤ 2 integrins to modulate their adhesive functions and with the ␤ 2 integrin, CR3 (CD11b/CD18), to trigger urokinase plasminogen activator-induced Ca 2ϩ fluxes in neutrophils (32,33). More recently, a signaling partnership between uPAR and L-selectin (CD62L) was also demonstrated in human polymorphonuclear neutrophils (34). More importantly, recent evidence suggests that C1q and mannose-binding lectin can engage cell surface calreticulin (cC1q-R) and CD91 to initiate macropinocytosis and uptake of apoptotic cells (35).…”

Section: Discussionmentioning

confidence: 99%

Cooperation of C1q Receptors and Integrins in C1q-Mediated Endothelial Cell Adhesion and Spreading

Feng¹,

Tonnesen²,

Peerschke

et al. 2002

The Journal of Immunology

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The interaction of C1q with endothelial cells elicits a multiplicity of biologic responses. Although these responses are presumed to be mediated by the interaction of C1q with endothelial cell surface proteins, the identity of the participants is not known. In this study we examined the roles of two C1q binding proteins, cC1q-R/calreticulin and gC1q-R/p33, in C1q-mediated adhesion and spreading of human dermal microvascular endothelial cells (HDMVEC). When HDMVEC were cultured in microtiter plate wells coated with concentrations of C1q ranging from 0 to 50 μg/ml, a specific and dose-dependent adhesion and spreading was observed. The extent of adhesion and spreading was similar to the adhesion seen on collagen-coated wells. Spreading (68 ± 12%) and to a moderate extent adhesion (47 ± 9%) were inhibited by anti-gC1q-R mAb 60.11. Similar effects were noted with polyclonal anti-cC1q-R but not with control nonimmune IgG. The two Abs had a slight additive effect (75 ± 13% inhibition) when mixed together in the proportion of 100 μg/ml anti-gC1q-R and 30 μg/ml anti-cC1q-R. More importantly, a 100% inhibition of spreading, but not adhesion, to C1q-coated wells was observed when HDMVEC were cultured in the presence of 30 μM of the peptide GRRGDSP but not GRRGESP. Furthermore, while anti-β1 integrin Ab blocked both adhesion and spreading, anti-α5 integrin blocked only spreading and not adhesion. Ag capture ELISA of endothelial cell membrane proteins using polyclonal anti-gC1q-R showed the presence of not only β1 and α5 integrins but also CD44. Taken together these results suggest that endothelial cell adhesion and spreading require the cooperation of both C1qRs and β1 integrins and possibly other membrane-spanning molecules.

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Cutting Edge: Evidence for a Signaling Partnership Between Urokinase Receptors (CD87) and L-Selectin (CD62L) in Human Polymorphonuclear Neutrophils

Cited by 46 publications

References 28 publications

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

Cutting Edge: Antigen-Driven Lymphocyte Recruitment to the Lung Is Diminished in the Absence of Urokinase-Type Plasminogen Activator (uPA) Receptor, but Is Independent of uPA

Urokinase-type plasminogen activator induces proliferation in breast cancer cells

Cooperation of C1q Receptors and Integrins in C1q-Mediated Endothelial Cell Adhesion and Spreading

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