Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion

Jun, Chang‐Duk; Shimaoka, Motomu; Carman, Christopher V.; Takagi, Junichi; Springer, Timothy A.

doi:10.1073/pnas.121186998

Cited by 67 publications

(42 citation statements)

References 47 publications

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“…Our present results with acidic/basic leucine 'zipped' E-cadherin dimers show that the integrin engages only one of the two EC1 domains available in dimeric E-cadherin. This contrasts with results from similar experiments with LFA-1 and ICAM-1 which showed that dimeric ICAM-1 can bind two LFA-1 molecules [38]. Our present finding is explained by a recent NMR study on E-cadherin dimerization [29].…”

Section: Discussioncontrasting

confidence: 99%

“…Three versions were used: dimeric E-cadherin-Fc previously described [30], an E-cadherin dimer in which the E-cadherin chain was fused to an acidic/ basic coiled coil leucine zipper [38,43] and, E-cadherin monomer in which EC1-5 was fused to the basic component of the zipper. DNA for the basic and acidic sides of the zipper, was prepared by annealing and filling in two overlapping oligonucleotides.…”

Section: Dna Constructionsmentioning

confidence: 99%

“…Ca 2+ , Mg 2+ and Mn 2+ were used at 1 mM each and in some experiments PMA (15 ng/ml) was present. Acidic/basic leucine zipped dimers were attached to assay plates using antibody 2H11 [38,43] which is specific for the dimerized zipper. For experiments comparing monomeric and dimeric Ecadherin, both species were attached to the assay plate using mAb DECMA-1 which is specific for E-cadherin EC4.…”

Section: Cell Adhesion Testsmentioning

confidence: 99%

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Role of the αI domain in ligand binding by integrin αEβ7

et al. 2003

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The I domain of integrin § E was modeled on the crystal structure of that in CD11b and mutated to produce an open (high affinity) or closed (low affinity) conformation. K562 transfectants expressing mutant § E and wild-type g 7 were tested for adhesion to E-cadherin-Fc. Downward displacement of the C terminus of the § I domain with a disulfide bridge enhanced adhesion and Mn 2+ dependency. Adhesion greatly exceeded that observed using wild type integrin under similar conditions. The closed integrin gave poor adhesion which was greatly improved by PMA-induced clustering. Blocking g 7 function with a g I domain-specific antibody inhibited the wild-type but not the locked open integrin. Isolated open § I domain expressed on K562 cells showed strong Mn 2+ -dependent adhesion to E-cadherin, whereas the wild-type version was ineffective. § E g 7 was shown to bind to monomeric E-cadherin but to only one component of dimeric E-cadherin. Finally, we report that M290, a functionblocking antibody, bound to a conformation-sensitive epitope near the rim of the § I domain MIDAS and recognized wild-type and closed § I domain but not the open conformation. The results broadly support the paradigm for affinity regulation by conformational change that has been established for g 2 integrins. Nevertheless, for § E, the fully open conformation may represent an extreme situation that does not occur physiologically.

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Section: Discussioncontrasting

confidence: 99%

Section: Dna Constructionsmentioning

confidence: 99%

Section: Cell Adhesion Testsmentioning

confidence: 99%

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Role of the αI domain in ligand binding by integrin αEβ7

et al. 2003

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“…6, C and D). A possible interpretation for this contrast is the different surface expressions of ICAM-1 molecules, because the combination of monomeric and dimeric ICAM-1 isoforms should not necessarily be identical between two types of cells, and the different presentation of those isoforms would yield distinct binding kinetics (43)(44)(45). The difference of body stiffness and surface microtopology between WM9 and HPMEC cells may also significantly affect the twodimensional binding kinetics (22,46).…”

Section: Figure 7 Binding Curve Of Pmns Adhesion To Quiescent Mda-mbmentioning

confidence: 99%

Determining β2-Integrin and Intercellular Adhesion Molecule 1 Binding Kinetics in Tumor Cell Adhesion to Leukocytes and Endothelial Cells by a Gas-driven Micropipette Assay

Tong

Wang

et al. 2011

Journal of Biological Chemistry

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Interactions between polymorphonuclear neutrophils (PMNs) and tumor cells have been reported to facilitate the adhesion and subsequent extravasation of tumor cells through the endothelium under blood flow, both of which are mediated by binding ␤ 2 -integrin to intercellular adhesion molecule 1 (ICAM-1). Here the adhesions between human WM9 metastatic melanoma cells, PMNs, and human pulmonary microvascular endothelial cells (HPMECs) were quantified by a gas-driven micropipette aspiration technique (GDMAT). Our data indicated that the cellular binding affinity of PMN-WM9 pair was 3.9-fold higher than that of the PMN-HPMEC pair. However, the effective binding affinities per molecular pair were comparable between the two cell pairs no matter whether WM9 cells or HPMECs were quiescent or cytokine-activated, indicating that the stronger adhesion between PMN-WM9 pair is mainly attrib- Tumor metastasis requires the detachment of malignant cells from primary tumor, invasion through blood/lymph vessels, transmigration across the endothelium, and finally, adhesion to the host cells (1). The adhesion and subsequent extravasation of tumor cells through the vascular endothelium are critical steps in this complex cascade (2). Malignant melanoma is the most deadly skin cancer with high metastatic potential (3). Although the binding of such adhesion molecules as P-selectin (4, 5), Lu-ECAM-1 (6), or integrin ␣ 4 ␤ 1 (VLA-4) (7) to their ligands has been found to support the adhesion of melanoma tumor cells (TCs) 3 with endothelial cells (ECs), the expression of the molecules seems insufficient to support the direct adhesion between TCs and ECs in blood flow (8). Rather, the presence of polymorphonuclear neutrophils (PMNs) potentially enhances TCs adhesion to the ECs and induces the subsequent extravasation under flow conditions (9 -11). A "two-step adhesion" hypothesis was introduced that involves initial PMN tethering on ECs followed by subsequent TCs being captured by tethered PMNs (10). Another line of in vitro evidence has indicated independently that TCs are able to aggregate with PMNs in a shear flow (12), which proposes an alternative hypothesis that TCs interact first with PMNs to form aggregates in a near-wall region of vascular endothelium prior to binding to EC through PMNs. Thus, it is physiologically important to elucidate how TCs, PMNs, and/or ECs interact with each other and what their underlying molecular mechanisms are.Regulations of PMN-EC or PMN-TC adhesion have been extensively studied at the cellular and molecular levels. Tethering and rolling of leukocytes on the endothelium are initiated by selectins and stabilized by ␤ 2 -integrins, which is followed by PECAM-1-induced transmigration through the extracellular matrix (13,14). Tumor cells are found to interact with PMNs under shear flow in a cone-plate viscometer (12,(15)(16)(17). Evidently, the interactions between ␤ 2 -integrin (LFA-1 or Mac-1) expressed on PMNs and intercellular adhesion molecule 1 (ICAM-1) expressed on TCs or ECs dominate both PMN-EC a...

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“…ICAM-1, a counter-receptor for integrins on WBC, supports their firm adhesion to EC and thus contributes to inflammation [97][98][99][100]. In addition, ICAM-1 serves as a natural ligand for certain viruses [101].…”

Section: Similar To Abovementioning

confidence: 99%

Targeting of Drugs to ICAM for Treatment of Acute Lung Injury

Muzykantov¹

2004

PsycEXTRA Dataset

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_ Public reporting burden for this coliection of information is estimated to average 1 tiour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining " the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing Uiis bunjen to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highv^ay, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Papenrork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank) REPORT DATE April 2004 REPORT TYPE AND DATES COVERED Annual (11 Mar 2003 -10 Mar 2004) TITLE AND SUBTITLE Targeting of Drugs to ICAM for Treatment of Acute Lung Injury AUTHOR(S)Vladimir Muzykantov, Ph.D. FUNDING NUMBERS DAMD17-02-1-0197 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Pennsylvania Philadelphia, PA 19104-6205 E-Mail: muzykantOmail. med. upenn. edu PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSORING / MONITORING AGENCY REPORT NUMBER SUPPLEMENTARY NOTESOriginal contains color plates: ALL DTIC reproductions will be in black and white 12a. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words)In the second year, we characterized intracellular traffic and final destination of anti-CAM conjugates in endothelial cells (EC) and found that CAM-mediated endocytosis initiates an unusually slow vesicular traffic that delivers conjugates to lysosomes several hours after internalization. Further, auxiliary drugs that regulate these processes can be utilized for prolongation of therapeutic duration of internalized conjugates. We characterized a series of in-house models of human ALI (injection of anti-TM/GOX and hyperoxia in mice), studied dynamics and role of EC cell adhesion molecules and leukocytes in these models and developed a new, clinically relevant and reliable model of ALI, based on combined treatment with anti-TM/GOX and hyperoxia. We synthesized anti-CAM/SOD conjugate with proper targeting size (~200 nm), enzymatic activity and affinity to EC and documented that it accumulates in the pulmonary vasculature after intravenous injection, thus satisfying main requirements for subsequent testing in animal models of ALI. In vitro and in vivo fibrinolysis studies have been employed in order to select the optimal candidate fibrinolytic (a novel tPA derivative, Tenektase) for targeting to endothelial CAM. Design and production of optimized affinity carriers for this purpose is in progress. SUBJECT TERMSEndothelium, immunotargeting, oxidant stress, thrombosis, ICAM-1 Vladimir Muzykantov, PI, DAMD 17-02-1-0197 "ICAM Targeting in Acute Lung Injury" Second Annual ...

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Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion

Cited by 67 publications

References 47 publications

Role of the αI domain in ligand binding by integrin αEβ7

Role of the αI domain in ligand binding by integrin αEβ7

Determining β2-Integrin and Intercellular Adhesion Molecule 1 Binding Kinetics in Tumor Cell Adhesion to Leukocytes and Endothelial Cells by a Gas-driven Micropipette Assay

Targeting of Drugs to ICAM for Treatment of Acute Lung Injury

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