Related Experiment Video
Updated: May 10, 2026
12:04
The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
The CD11b-integrin (ITGAM) and systemic lupus erythematosus
S C Fagerholm1, M MacPherson, M J James
1Medical Research Institute, Ninewells Hospital and Medical School, Institute of Biotechnology, University of Helsinki, Finland. s.c.fagerholm@dundee.ac.uk
Lupus
|June 12, 2013
Summary
Genetic variations in the ITGAM gene, specifically rs1143679, are linked to systemic lupus erythematosus (SLE). This variant causes a dysfunctional Mac-1 integrin, impairing immune cell functions and potentially contributing to SLE development.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- The ITGAM gene encodes the CD11b chain of the Mac-1 integrin, a key immune cell receptor.
- Genetic variations in ITGAM are strongly associated with systemic lupus erythematosus (SLE) risk.
- A specific variant, rs1143679, leads to an arginine-to-histidine substitution in the Mac-1 integrin.
Purpose of the Study:
- To review the immunological functions of the Mac-1 integrin.
- To explore how genetic defects in Mac-1 may contribute to the development of SLE.
- To understand the functional consequences of the rs1143679 variant.
Main Methods:
- Review of existing literature on ITGAM gene, Mac-1 integrin function, and SLE.
- Analysis of the functional impact of the arginine-to-histidine substitution at position 77.
- Discussion of cellular adhesion, phagocytosis, and cytokine regulation by Mac-1.
Main Results:
- The rs1143679 variant results in a dysfunctional Mac-1 integrin.
- This dysfunctional integrin shows deficiencies in cell adhesion and phagocytosis.
- The variant also impairs the ability to restrict inflammatory cytokine production in macrophages.
Conclusions:
- Defects in the Mac-1 integrin due to ITGAM gene variations are implicated in SLE pathogenesis.
- The rs1143679 variant's functional impairments provide a mechanistic link to SLE development.
- Understanding these genetic and functional links is crucial for SLE research.
Related Concept Videos
01:31Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:25Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.