ArticlePloS one2013
Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 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
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- The guardians of pulmonary harmony: alveolar macrophages orchestrating the symphony of lung inflammation and tissue homeostasis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- The Role of Genetic Risk Factors in Pathogenesis of Childhood-Onset Systemic Lupus Erythematosus.Current issues in molecular biology · 2023Review
- Targeting Neutrophil βBiomolecules · 2023Review
- Targeting DAMPs with nucleic acid scavengers to treat lupus.Translational research : the journal of laboratory and clinical medicine · 2022Review
- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- [Immune Modulatory Effect of Outer Membrane Vesicles Derived fromSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Alveolar Macrophages in Influenza A Infection Guarding the Castle with Sleeping Dragons.Infectious diseases and therapeutics · 2020Article
- 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
- Article
- Significance of Complement System in Ischemic Stroke: A Comprehensive Review.Aging and disease · 2019Review
- Association of the CD11b rs1143679 polymorphism with systemic lupus erythematosus in the Han Chinese population.The Journal of international medical research · 2018Article
- Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells.Journal of visualized experiments : JoVE · 2018Article
- Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn-SIRPα-SHP1 complex.Experimental & molecular medicine · 2018Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis.
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