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The human C3b receptor: function and role in human diseases
1Division of Dermatology, University of California, School of Medicine, San Diego 92103.
Insights
The human complement receptor 1 (CR1) regulates the complement system and aids in clearing immune complexes. Reduced CR1 on erythrocytes in diseases like AIDS may impair immune complex clearance.
Area of Science:
- Immunology
- Complement System Biology
Background:
- The human complement receptor 1 (CR1) is a polymorphic glycoprotein crucial for regulating the complement system.
- CR1 acts as a cofactor for factor I, degrading complement fragments like C3b.
- Erythrocyte-bound CR1 (CR1/E) facilitates immune complex (IC) clearance via the reticuloendothelial system.
Purpose of the Study:
- To elucidate the multifaceted roles of CR1 in immune regulation and clearance.
- To investigate the variations in CR1 expression and its clinical implications in various diseases.
Main Methods:
- The study reviews the known functions of CR1 in complement regulation and immune complex handling.
- It discusses the inherited variations in CR1 expression on erythrocytes (CR1/E).
- The abstract examines the decrease in CR1/E observed in diseases with elevated IC levels, such as systemic lupus erythematosus, leprosy, and AIDS.
Main Results:
- CR1 inhibits complement activation (C3 and C5) and mediates C3b degradation.
- CR1 on erythrocytes facilitates immune complex transport and clearance.
- Reduced CR1/E levels correlate with disease activity in conditions like AIDS, potentially impairing clearance.
- Neutrophils exhibit increased CR1 expression upon stimulation, a response altered in AIDS patients.
Conclusions:
- CR1 plays a vital role in both complement system regulation and immune complex clearance.
- Inherited variations and disease-associated reductions in CR1/E can compromise immune complex handling.
- Altered CR1 expression and function in neutrophils may impact phagocytosis in diseases like AIDS.
Abstract:
The human C3b receptor (CR1) is a polymorphic glycoprotein which functions regulating the complement system by inhibiting the activation of C3 and C5, through its effect on their convertases, and serving as cofactor for factor I in mediating the degradation of C3b to its inactive fragment C3bi and further to C3d-g. The latter are then ligands for their respective receptors on leukocytes, CR3 and CR2. Additionally, CR1 on erythrocytes endows these cells with the capacity to deliver immune complexes (IC) to the reticuloendothelial system, resulting in their clearance from the circulation. On phagocytes, this receptor participates in the process of endocytosis of foreign particles. There is a wide inherited variation of CR1 expression on erythrocytes (CR1/E) of different individuals. Patients with diseases which feature elevated levels of IC, such as systemic lupus erythematosus, leprosy, and AIDS, have a marked decrease of CR1/E, which may result in an altered clearance. This reduction appears to be related to disease activity, and the most probable site for CR1/E loss is during the transfer of IC to macrophages. Healthy neutrophils increase tenfold their expression of CR1 in response to the effect of chemoattractant peptides. Neutrophils from patients with AIDS display an altered response to stimulation. This defect may be of relevance in the process of endocytosis.