CD14

CD14 exists in two forms: a membrane-bound form (mCD14) anchored via GPI on monocytes, macrophages, and neutrophils, and a soluble form (sCD14) found in serum. When gram-negative bacteria release LPS (endotoxin) from their outer membrane, LPS-binding protein (LBP) in plasma binds LPS and transfers it to CD14. CD14 lacks a transmembrane signaling domain, so it functions as a co-receptor that presents LPS to the TLR4/MD-2 complex, which then signals through MyD88-dependent and independent pathways to activate NF-κB, leading to production of pro-inflammatory cytokines (TNF-α, IL-1, IL-6). This cascade is central to the pathophysiology of septic shock caused by gram-negative bacteria, where excessive CD14/TLR4 activation leads to a cytokine storm, vasodilation, capillary leak, hypotension, and disseminated intravascular coagulation (DIC). CD14 is also used as a diagnostic/flow cytometry marker to identify monocytes and macrophages (CD14+ cells) and is relevant in distinguishing monocytic lineage in leukemias (e.g., acute monocytic leukemia, AML M5). Clinically, understanding CD14's role helps explain the mechanism of endotoxin-mediated septic shock and is relevant to sepsis pathophysiology questions on USMLE Step 1. High-yield associations: CD14 + LBP + TLR4/MD-2 = LPS recognition complex; gram-negative sepsis; monocyte/macrophage marker.