We hypothesized that the deleterious effect of anti-ICAM-1 antibody in the Enlimomab trial that overwhelmed any potential benefit from inhibition of leukocyte accumulation was due to the augmentation of ischemic brain injury by the immunogenicity of Enlimomab.
What are the applications of antibodies that detect ICAM-1?
Antibodies that detect ICAM-1 (CD54) can be used in several scientific applications, including Flow Cytometry, Western Blot, Immunohistochemistry (Paraffin), Immunocytochemistry ... View more
Can ICAM-1 block virus-receptor binding to prevent rhinovirus infection?
The majority of HRVs use a single cellular receptor, ICAM-1, for attachment to cells and therefore ICAM-1 is an interesting target to block virus-receptor binding to prevent rhinovirus infection. Several alternative approaches have been investigated, but have not been taken further in clinical trials or had to be abandoned because of side effects.
What is the abbreviation for ICAM1?
ICAM-1 (CD54) Antibodies. ICAM-1 (CD54) is an 85-110 kDa single-chain type 1 integral membrane glycoprotein with an extracellular domain of five immunoglobulin superfamily ... View more. Synonyms. CD54; cell surface glycoprotein P3.58; ICAM-1; Intercellular adhesion molecule 1; intercellular adhesion molecule 1 (CD54), ...
Is anti-ICAM therapy with enlimomab an effective treatment for stroke?
The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial Neurology.
What does anti ICAM antibody therapy do?
These findings suggest that anti-ICAM-1 antibody is quite useful for delaying the occurrence of graft rejection in the early stage. Electron microscopic examination demonstrated the same results as conventional HE staining.
Is ICAM an immunoglobulin?
ICAM-1 is a member of the immunoglobulin superfamily, the superfamily of proteins including antibodies and T-cell receptors.
What is the role of the adhesion molecule ICAM during inflammation?
Intercellular adhesion molecule-1 (ICAM-1) is up-regulated during inflammation by several cell types. ICAM-1 is best known for its role in mediating leukocyte adhesion to endothelial cells and guiding leukocytes across the vascular wall.
Is ICAM on T cells?
The role of ICAM-1 has been considered primarily as an LFA-1 ligand on cells with which T cells interact. However, a signaling role has been identified for ICAM-1 in T cells (18), B cells (16, 17), and endothelial cells (15).
What does ICAM stand for?
Integrated Computer Aided Manufacturing. ICAM. Integrated Computer-Aided Manufacturing.
How do I set up ICAM?
Video: Simple remote video surveillanceStep 1: Set up iCam on your computer(s) Head to http://skjm.com/icam/support.php and download iCamSource for Mac or PC. ... Step 2: Install iCam on your Android or iOS device. With your cameras set up, you're ready to start remotely viewing the surveillance with your mobile device.
What is VCAM and ICAM?
Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are endothelial CAMs of the immunoglobulin (Ig) superfamily with a critical role in mediating the firm adhesion of leukocytes to endothelial cells in various acute and chronic inflammatory diseases.
Why does leukocyte adhesion happen?
Leukocyte adhesion syndromes are rare, genetic disorders. LAD I is caused by mutations of the ITGB2 gene. LAD II is caused by mutations of the SLC35C1 gene. The genetic defect in LAD III is a mutation in the gene for Kindlin 3, a protein essential for all integrins activation.
What is endothelial adhesion?
Platelet–Endothelial Adhesion. In some forms of inflammation, the accumulation of platelets within the microvasculature appears to result from a direct interaction between platelets and vascular ECs.
What is ICAM immunology?
The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells.
What does LFA-1 stand for?
Lymphocyte Function Associated Antigen 1The leukocyte function associated antigen 1 (LFA-1) is a member of the heterodimeric B2 integrin family and consists of a noncovalently linked unique alpha chain (CD11a) and a beta chain (CD18).
What does LFA-1 bind to?
Upon recognition of a target antigen via TCR/pMHC complex formation, CD8+ T cell activates LFA-1 and binds to ICAM-1 expressed on the target cell. Important functions of LFA-1 during the cytotoxic response was demonstrated with LFA-1 blockers that inhibited target cell killing (107–109).
What is the role of ICAM-1?
ICAM-1 plays an important role in trans-endothelial migration of leukocytes and activation of T cells via LFA-1 . In addition it is also the entry receptor for major group HRVs. We were interested in identifying antibodies suitable to inhibit HRV-ICAM-1 interactions for the potential treatment of HRV-induced exacerbations in airway disease without compromising the host leukocyte trafficking by interference of ICAM-1 interactions with the integrin LFA-1. We thus initially investigated the binding properties of the commercially available antibodies to human ICAM-1 - 14C11 and 84H10 - to determine whether they bind to domain 1 of human ICAM-1 (Hu ICAM-1) the putative binding site for viral entry [2], [16]. Biotinylated Hu ICAM-1, a chimeric protein consisting of domain 1 of human ICAM-1 and domains 2–5 of mouse ICAM-1 (Hu1 Mu2-5), murine ICAM-1 (Mu ICAM-1) and insulin as a control protein were incubated with 14C11 or 84H10 to test their binding specificity. We found binding of 14C11 and 84H10 to both Hu ICAM-1 and Hu1 Mu2-5 confirming that 14C11 binds specifically to domain 1 of human ICAM-1, but not to murine ICAM-1 (Figure 1A and 1B). Additionally, cells were stimulated with PMA in a human T cell (Jurkat cell) adhesion assay, to determine whether 14C11 or 84H10 could inhibit human ICAM-1/LFA-1 interactions. Neither 14C11 nor the isotype control was able to prevent cell adhesion via LFA-1 whereas the anti-ICAM-1 antibody 84H10 blocked the ICAM-1/LFA-1 interaction and failed to retain the labelled Jurkat cells (Figure 1C). These results emphasise that the domain specificity of 14C11 suggests it will not block human ICAM-1/LFA-1 interaction. Regarding binding to other members of the immumoglobulin (Ig) superfamily structurally related to huICAM-1 the specification provided by the manufacturer stated that 14C11 showed no cross-reactivity with rabbit ICAM-1, human ICAM-2, human ICAM-3, human VCAM-1, and ‘mouse DCC’. We also demonstrated the binding specificity of 14C11 observing binding to human ICAM-1 and a chimeric mouse ICAM-1 with domain 1 substituted for human ICAM-1 Ig domain 1. In the same assay no binding to mouse ICAM-1, human ICAM-2, human ICAM-3, human ICAM-5 or human VCAM-1 was observed. (Fig. S1).
Does 14C11 inhibit ICAM-1?
We also show that this antibody does not inhibit human ICAM-1/LFA-1 interactions and therefore should not interfere with cellular trafficking.
What is the ICAM-1?
ICAM-1 (CD54) is an 85-110 kDa single-chain type 1 integral membrane glycoprotein with an extracellular domain of five immunoglobulin superfamily repeats , a transmembrane region and a cytoplasmic domain. ICAM-1 has 7 potential N-linked glycosylation sites and shares considerable amino acid sequence homology with ICAM-3 (CD50) and ICAM-2 (CD102). ICAM-1 binds to integrins of type CD11a/CD18 (leukocyte adhesion molecule, LFA-1), or CD11b/CD18 (Mac-1) and is exploited by Rhinovirus as a receptor. ICAM-1 is expressed by activated endothelial cells and detected on epithelial cells, fibroblasts, chondrocytes, B lymphocytes, T lymphocytes (low), monocytes, macrophages, dendritic cells and neutrophils, with lower levels that increase upon inflammation. ICAM-1 is also detected in some carcinoma and melanoma cells. Soluble ICAM-1 is detectable in the plasma and is elevated in patients with various inflammatory syndromes.
Which cells are ICAM-1 expressed in?
ICAM-1 is expressed by activated endothelial cells and detected on epithelial cells, fibroblasts, chondrocytes, B lymphocytes, T lymphocytes (low), monocytes, macrophages, dendritic cells and neutrophils, with lower levels that increase upon inflammation. ICAM-1 is also detected in some carcinoma and melanoma cells.
Is ICAM-1 detectable in plasma?
ICAM-1 is also detected in some carcinoma and melanoma cells. Soluble ICAM-1 is detectable in the plasma and is elevated in patients with various inflammatory syndromes. Synonyms. CD54; cell surface glycoprotein P3.58; ICAM-1; Intercellular adhesion molecule 1; intercellular adhesion molecule 1 (CD54), human rhinovirus receptor;
What is the role of ICAM-1?
ICAM-1 plays an important role in trans-endothelial migration of leukocytes and activation of T cells via LFA-1 . In addition it is also the entry receptor for major group HRVs. We were interested in identifying antibodies suitable to inhibit HRV-ICAM-1 interactions for the potential treatment of HRV-induced exacerbations in airway disease without compromising the host leukocyte trafficking by interference of ICAM-1 interactions with the integrin LFA-1. We thus initially investigated the binding properties of the commercially available antibodies to human ICAM-1 - 14C11 and 84H10 - to determine whether they bind to domain 1 of human ICAM-1 (Hu ICAM-1) the putative binding site for viral entry [2], [16]. Biotinylated Hu ICAM-1, a chimeric protein consisting of domain 1 of human ICAM-1 and domains 2–5 of mouse ICAM-1 (Hu1 Mu2-5), murine ICAM-1 (Mu ICAM-1) and insulin as a control protein were incubated with 14C11 or 84H10 to test their binding specificity. We found binding of 14C11 and 84H10 to both Hu ICAM-1 and Hu1 Mu2-5 confirming that 14C11 binds specifically to domain 1 of human ICAM-1, but not to murine ICAM-1 ( Figure 1A and 1B ). Additionally, cells were stimulated with PMA in a human T cell (Jurkat cell) adhesion assay, to determine whether 14C11 or 84H10 could inhibit human ICAM-1/LFA-1 interactions. Neither 14C11 nor the isotype control was able to prevent cell adhesion via LFA-1 whereas the anti-ICAM-1 antibody 84H10 blocked the ICAM-1/LFA-1 interaction and failed to retain the labelled Jurkat cells ( Figure 1C ). These results emphasise that the domain specificity of 14C11 suggests it will not block human ICAM-1/LFA-1 interaction. Regarding binding to other members of the immumoglobulin (Ig) superfamily structurally related to huICAM-1 the specification provided by the manufacturer stated that 14C11 showed no cross-reactivity with rabbit ICAM-1, human ICAM-2, human ICAM-3, human VCAM-1, and ‘mouse DCC’. We also demonstrated the binding specificity of 14C11 observing binding to human ICAM-1 and a chimeric mouse ICAM-1 with domain 1 substituted for human ICAM-1 Ig domain 1. In the same assay no binding to mouse ICAM-1, human ICAM-2, human ICAM-3, human ICAM-5 or human VCAM-1 was observed. ( Fig. S1 ).
What is 14C11 antibody?
Moreover 14C11 is a mouse anti-human IgG1 type antibody and could potentially bind to mouse Fcγ receptors on innate immune cells, such as FcγRIIB, providing a potential inhibitory signal. To investigate whether the 14C11 antibody non-specifically inhibited inflammation by cross-linking human ICAM-1 and binding Fcγ receptor cells we therefore investigated whether 14C11 could inhibit cellular inflammation evoked in tg+ mice, but by a non human ICAM-1 mediated infection using minor group HRV1B infection. Transgenic negative and transgenic positive littermates were dosed intravenously 24 hours prior to viral infection with or without 20 mg/kg isotype control or 14C11 antibody and consequently infected with UV-inactivated HRV1B or with HRV1B. Significant induction of total BAL cells and neutrophils at day 1 post infection and lymphocyte numbers at day 4 could be observed compared to mice infected with UV-inactivated HRV1B in both types of mice ( Figure 5A ). Induction by HRV1B of each cell type was virtually identical in tg+ and tg− mice, suggesting that the transgenic over-expression of the chimeric human/mouse ICAM-1 molecule did not influence cell trafficking via potential interactions with mouse LFA-1.
What is the specificity of 14C11?
The antibody 14C11 is specific for domain 1 of human ICAM1 and does not cross-react with other ICAM family members. To determine antibody specificity 14C11 was tested for binding to a panel of ICAM family members. Using an ELISA 14C11 was incubated with human (Hu) ICAM1, Mouse ICAM1, Hu ICAM-2, -3, -5 and Hu VCAM1. In addition a chimeric protein consisting of human ICAM1 domain 1 (Hu D1) and mouse domains 2 to 5 (Mu D2-5) was evaluated. Specific anti-ICAM-2, -3, -5 and VCAM1 antibodies were used as positive controls. Recombinant insulin was also used as a negative control to determine non-specific binding.
Does 14C11 prevent cell adhesion?
Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.
Does 14C11 inhibit replication?
Next we tested the effect of 14C11 in an in vitro HRV infection assay. Using a cytopathic effect assay (CPE) we showed the antiviral effect of 14C11 in inhibiting the replication of HRV16 ( Figure 2A) and HRV14 ( Figure 2B) with increasing concentration of antibody. 14C11 did not inhibit CPE caused by infection with minor group serotype HRV25 ( Figure 2C) consistent with ICAM-1 blockade-specific mechanism of action. Isotype control antibody did not prevent replication of HRV16 or HRV14 in HeLa Ohio cells. Additionally, the median tissue culture inhibitory concentration (IC 50) was assessed for a wide range of major group HRVs as indicated in Figure 2D, suggesting a consistent prevention of replication by 14C11 for many major type HRVs, the great majority with sub-nanoMolar IC 50 s. These results emphasise that the domain specificity of 14C11 indicates it inhibits human ICAM-1-HRV binding but does not block human ICAM-1/LFA-1 interaction.
