ArticleBiochimica et biophysica acta2013
Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Gut microbiota dysbiosis aggravates sepsis-induced lung injury by promoting neutrophil extracellular traps and suppressing host integrin defense.Frontiers in microbiology · 2025Article
- The integrin CD11b inhibits MSU-induced NLRP3 inflammasome activation in macrophages and protects mice against MSU-induced joint inflammation.Arthritis research & therapy · 2024Article
- Conjecturing about Small-Molecule Agonists and Antagonists of α4β1 Integrin: From Mechanistic Insight to Potential Therapeutic Applications.Biomedicines · 2024Review
- Targeting Neutrophil βBiomolecules · 2023Review
- Design and Pharmacological Characterization of αJournal of medicinal chemistry · 2023Article
- The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses.Frontiers in immunology · 2023Article
- Dock2 generates characteristic spatiotemporal patterns of Rac activity to regulate neutrophil polarisation, migration and phagocytosis.Frontiers in immunology · 2023Article
- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- GB1275, a first-in-class CD11b modulator: rationale for immunotherapeutic combinations in solid tumors.Journal for immunotherapy of cancer · 2021Review
- Deficiency of ITGAM Attenuates Experimental Abdominal Aortic Aneurysm in Mice.Journal of the American Heart Association · 2021Article
- The Promiscuous Profile of Complement Receptor 3 in Ligand Binding, Immune Modulation, and Pathophysiology.Frontiers in immunology · 2021Review
- Identification of Oleanolic Acid as Allosteric Agonist of Integrin αFrontiers in pharmacology · 2021Article
- A Genetic Model of Constitutively Active Integrin CD11b/CD18.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Monoclonal Antibody to CD14, TLR4, or CD11b: Impact of Epitope and Isotype Specificity on ROS Generation by Human Granulocytes and Monocytes.Oxidative medicine and cellular longevity · 2020Review
- Protective Effects of Leukadherin1 in a Rat Model of Targeted Experimental Autoimmune Encephalomyelitis (EAE): Possible Role of P47phox and MDA Downregulation.Journal of inflammation research · 2020Article
- Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies.Science translational medicine · 2019Article
- Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction.Frontiers in immunology · 2019Article
- Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from critically ill patients.Journal of intensive care · 2018Article
- Can Integrin Agonists Have Cards to Play against Cancer? A Literature Survey of Small Molecules Integrin Activators.Cancers · 2017Review
- Microglial complement receptor 3 regulates brain Aβ levels through secreted proteolytic activity.The Journal of experimental medicine · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCD11b/CD18 is a key adhesion receptor that mediates leukocyte adhesion, migration and immune functions. We recently identified novel compounds, leukadherins, that allosterically enhance CD11b/CD18-dependent cell adhesion and reduce inflammation in vivo, suggesting integrin activation to be a novel mechanism of action for the development of anti-inflammatory therapeutics. Since a number of well-characterized anti-CD11b/CD18 activating antibodies are currently available, we wondered if such biological agonists could also become therapeutic leads following this mechanism of action.
methodsWe compared the two types of agonists using in vitro cell adhesion and wound-healing assays and using animal model systems. We also studied effects of the two types of agonists on outside-in signaling in treated cells.
resultsBoth types of agonists similarly enhanced integrin-mediated cell adhesion and decreased cell migration. However, unlike leukadherins, the activating antibodies produced significant CD11b/CD18 macro clustering and induced phosphorylation of key proteins involved in outside-in signaling. Studies using conformation reporter antibodies showed that leukadherins did not induce global conformational changes in CD11b/CD18 explaining the reason behind their lack of ligand-mimetic outside-in signaling. In vivo, leukadherins reduced vascular injury in a dose-dependent fashion, but, surprisingly, the anti-CD11b activating antibody ED7 was ineffective.
conclusionsOur results suggest that small molecule allosteric agonists of CD11b/CD18 have clear advantages over the biologic activating antibodies and provide a mechanistic basis for the difference. GENERAL SIGNIFICANCE: CD11b/CD18 activation represents a novel strategy for reducing inflammatory injury. Our study establishes small molecule leukadherins as preferred agonists over activating antibodies for future development as novel anti-inflammatory therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.