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Human liver Kupffer cells express CR1, CR3, and CR4 complement receptor antigens. An immunohistochemical study
N Hinglais1, M D Kazatchkine, C Mandet
1INSERM U28, Hôpital Broussais, Paris, France.
Insights
Human Kupffer cells (KC) express complement receptors CR1, CR3, and CR4. This expression enhances their ability to bind and phagocytize immune complexes and particles, crucial for liver immunity.
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- Kupffer cells (KC) are resident macrophages in the liver sinusoids.
- KC play a critical role in innate immunity and liver homeostasis.
- The expression of complement receptors on KC is not fully characterized.
Purpose of the Study:
- To investigate the expression of complement receptor antigens on human Kupffer cells.
- To determine which complement receptors are predominantly expressed by KC.
- To understand the functional implications of complement receptor expression on KC.
Main Methods:
- Immunohistochemical techniques were used on normal human liver biopsies.
- Double labeling with indirect immunofluorescence and immunoenzymatic methods were employed.
- Monoclonal antibodies against complement receptors (CR1, CR2, CR3, CR4) and KC marker (EBM11) were utilized.
Main Results:
- Complement receptors CR1 and CR3 were predominantly expressed by human KC.
- CR4 was expressed on all KC, but with weaker staining compared to CR3.
- No significant expression of CR2 (CD 21) was detected on KC.
Conclusions:
- Human KC express CR1, CR3, and CR4, indicating a significant role for complement system in KC function.
- This expression pattern equips KC with the capacity to bind and phagocytose complement-opsonized particles and immune complexes.
- Understanding KC complement receptor expression is vital for comprehending liver immune responses and developing targeted therapies.
Abstract:
The expression of complement receptor antigens by human Kupffer cells (KC) was investigated by immunohistochemical techniques in seven normal human liver biopsies. Polyclonal and monoclonal antibodies were revealed by double labeling of cells using indirect immunofluorescence and immunoenzymatic techniques or by using double immunoenzymatic techniques. In most experiments, one antigen was revealed by streptavidin-biotin-peroxidase complexes whose reaction product was examined by light microscopy and the second antigen stained using the alkaline phosphatase antialkaline phosphatase method visualized by fluorescence microscopy using fluorescein isothiocyanate or tetramethylrhodamine isothiocyanate filters. KC were identified using monoclonal antibody EBM11 that recognizes 100% of KC in hepatic lobules and was paired with each antibody directed against complement receptors. CR1 and CR3 (alpha- and beta-chains) were found to be the predominant receptor antigens expressed by human KC. CR4 (p150,95) was expressed on all KC, but staining with anti-CR4 monoclonal antibodies was consistently weaker than that observed with anti-CR3 antibodies. No staining of KC was observed with anti-CR2 (CD 21) antibodies. Expression of CR1, CR3, and CR4 complement receptors on KC provides the cells with an optimal capacity to bind and phagocytize particles or immune complexes coated with any type of ligands for C3 receptors.