ArticleThe Journal of biological chemistry2011
A systemic lupus erythematosus-associated R77H substitution in the CD11b chain of the Mac-1 integrin compromises leukocyte adhesion and phagocytosis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without.BMC medical genomics · 2016Pooled it
- Association between the functional ITGAM rs1143679 G/A polymorphism and systemic lupus erythematosus/lupus nephritis or rheumatoid arthritis: an update meta-analysis.Rheumatology international · 2015Pooled it
- How loss-of-function mutations inJournal of translational autoimmunity · 2026Review
- Three cryo-EM structures of complement C3d-bound αScience advances · 2026Article
- Large soluble CD18 complexes with exclusive ICAM-1-binding properties are shed during immune cell migration in inflammation.Journal of translational autoimmunity · 2025Article
- Determining Ligand Binding and Specificity Within the βBiomolecules · 2025Article
- Deletion of Tmem268 in mice suppresses anti-infectious immune responses by downregulating CD11b signaling.EMBO reports · 2024Article
- Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis.Journal of autoimmunity · 2024Article
- The 330 risk loci known for systemic lupus erythematosus (SLE): a review.Frontiers in lupus · 2024Article
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- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Lupus Nephritis: Current Perspectives and Moving Forward.Journal of inflammation research · 2022Review
- Dysfunction of complement receptors CR3 (CD11b/18) and CR4 (CD11c/18) in pre-eclampsia: a genetic and functional study.BJOG : an international journal of obstetrics and gynaecology · 2021Article
- Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- Exploring the etiopathogenesis of systemic lupus erythematosus: a genetic perspective.Immunogenetics · 2019Review
- Beta2-Integrins and Interacting Proteins in Leukocyte Trafficking, Immune Suppression, and Immunodeficiency Disease.Frontiers in immunology · 2019Review
- Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus in the Han Chinese population.The Journal of international medical research · 2018Article
- CD11b Activity Modulates Pathogenesis of Lupus Nephritis.Frontiers in medicine · 2018Review
- CD11b activation suppresses TLR-dependent inflammation and autoimmunity in systemic lupus erythematosus.The Journal of clinical investigation · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The Mac-1 integrin is expressed mainly on myeloid cells and binds several ligands, including members of the ICAM family and the complement factor iC3b. It is involved in essential immunological processes, such as leukocyte extravasation and phagocytosis. In addition, Mac-1 has been described to negatively regulate immune cell signaling. Recently, a single nucleotide polymorphism conferring an amino acid change in the Mac-1 integrin extracellular domain, R77H, was shown to be associated with systemic lupus erythematosus. Here, we demonstrate that the R77H-substituted Mac-1 can be expressed on the cell surface in transfected cells and can undergo conformational changes in response to integrin activation. The affinity of the integrin for ICAMs is only partially reduced, but cell adhesion to ICAM-1 and ICAM-2 is severely compromised, and Jβ2.7 cells expressing R77H substituted integrins are deficient in adhesion to ICAM-1 under shear flow conditions. Importantly, cell adhesion to the complement factor iC3b is also diminished, and COS cells expressing R77H-substituted integrins display reduced iC3b-dependent phagocytosis. In addition, U937 cells expressing R77H-CD11b display increased IL-6 production as compared with WT-CD11b-expressing cells. These results suggest that the R77H substitution results in the deficiency of the mutated integrin to mediate cell adhesion to ligands such as ICAMs and iC3b. These deficiencies may ultimately lead to detrimental effects on the immune system and contribute to the development of systemic lupus erythematosus.
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