CD14 - Cluster of Differentiation 14 | Elisa - Clia - Antibody - Protein

Background:

CD14, or Cluster of Differentiation 14, is a glycoprotein found on the surface of certain immune cells, primarily monocytes and macrophages. It plays a crucial role in the innate immune system, particularly in recognizing and responding to bacterial pathogens. CD14 acts as a receptor for lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria. It binds to LPS and facilitates the activation of cells such as macrophages and dendritic cells, triggering the production of pro-inflammatory cytokines and other immune responses. CD14 is a glycosylphosphatidylinositol (GPI)-anchored protein, meaning it is attached to the cell membrane via a glycolipid anchor. It consists of a single polypeptide chain with a molecular weight of approximately 55-60 kDa. Soluble forms of CD14 can be found in the bloodstream and other body fluids, where they can bind to circulating LPS. Activation of CD14-mediated signaling pathways leads to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). These cytokines play essential roles in initiating and regulating the inflammatory response to bacterial infection. Dysregulation of CD14 expression or function has been implicated in various inflammatory and infectious diseases. For example, excessive activation of CD14-mediated signaling pathways can contribute to the pathogenesis of sepsis, while deficiencies in CD14 expression or function may impair the host's ability to mount an effective immune response to bacterial infections.

Protein Structure:

• Primary Structure: CD14 is a glycoprotein consisting of 375 amino acids.
• Secondary and Tertiary Structures: The protein is rich in leucine-rich repeats (LRRs), which are crucial for its ability to bind LPS. The LRRs create a horseshoe-shaped solenoid structure that is essential for ligand recognition.
• Quaternary Structure: mCD14 is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. sCD14 lacks this anchor and circulates in the bloodstream.

Classification and Subtypes:

CD14 is classified as a pattern recognition receptor (PRR) and is part of the broader family of co-receptors that assist in the detection of pathogen-associated molecular patterns (PAMPs). The two main subtypes are:

• Membrane-bound CD14 (mCD14): Present on the surface of immune cells.
• Soluble CD14 (sCD14): Found in the bloodstream and other body fluids.

Function and Biological Significance:

• LPS Recognition: CD14 binds to LPS, a component of the outer membrane of Gram-negative bacteria. This binding is critical for the recognition of bacterial infections.
• Signal Transduction: CD14 forms a complex with TLR4 (Toll-like receptor 4) and MD-2, which triggers downstream signaling pathways leading to the production of pro-inflammatory cytokines.
• Immune Response Modulation: CD14 plays a role in modulating the inflammatory response, influencing both innate and adaptive immunity.

Interactions:

• Toll-Like Receptor 4 (TLR4): CD14 works closely with TLR4 and MD-2 to detect LPS and initiate immune signaling.
• LPS-Binding Protein (LBP): LBP facilitates the transfer of LPS to CD14, enhancing its ability to recognize bacterial components.
• MD-2: This molecule forms a complex with TLR4 and CD14, which is essential for LPS recognition and signal transduction.

Clinical Issues:

• Sepsis: Elevated levels of sCD14 are found in patients with sepsis and are associated with the severity of the condition. CD14 is implicated in the overwhelming inflammatory response seen in sepsis.
• Inflammatory Diseases: Aberrant CD14 signaling is involved in various inflammatory conditions, including autoimmune diseases, chronic inflammatory diseases, and atherosclerosis.
• Diagnostic Marker: sCD14 is used as a biomarker for several conditions, including infections, inflammation, and cardiovascular diseases.

Summary:

CD14 is a vital component of the immune system, serving as a co-receptor for the detection of bacterial LPS. Its role in immune signaling and inflammation makes it a key player in both normal immune responses and pathological conditions. Understanding the function and regulation of CD14 can provide insights into the mechanisms of immune activation and the development of therapeutic strategies for inflammatory diseases.