Neutrophils are a type of white blood cell and a primary component of the body’s innate immune system, serving as a first line of defense against pathogens. Markers are specific molecules on or within these cells that provide information about their identity, development stage, or functional state. These markers help clinicians understand neutrophil behavior and their role in various health conditions.
Understanding Neutrophils and Their Markers
Neutrophils are the most abundant white blood cell in humans, typically making up 50-70% of all leukocytes. These granulocytic cells have a multi-lobed nucleus and numerous cytoplasmic granules. Their primary function is to quickly respond to infection or inflammation by migrating to affected sites and eliminating pathogens.
Neutrophils possess various markers, including specific proteins, receptors, or enzymes on their cell surface or within their granules. These include adhesion molecules, such as CD11b and CD18, which help neutrophils stick to other cells. Activation markers, like CD66b, become more exposed when neutrophils are stimulated. Granule contents, such as myeloperoxidase (MPO) and elastase, are enzymes stored internally. Markers like CD15 and CD10 also indicate neutrophil maturation as they develop from bone marrow precursors.
Functional Roles of Key Neutrophil Markers
Adhesion molecules, such as selectins (L-, E-, and P-selectin) and integrins (e.g., Mac-1, composed of CD11b and CD18), are crucial for neutrophil recruitment to inflammation sites. Selectins mediate the initial weak attachment and rolling of neutrophils along blood vessel surfaces. Subsequently, chemokines activate integrins, leading to firm adhesion to the endothelium and migration into inflamed tissue.
Phagocytosis
Phagocytosis, the engulfment of pathogens, relies on receptors like Fc receptors (FcγRs) and complement receptors (CRs). FcγRs, such as FcγRIIa and FcγRIIIb, bind to antibody-coated pathogens, facilitating engulfment. Complement receptors, including CR1 (CD35) and CR3 (CD11b/CD18), recognize complement protein fragments that have marked pathogens for destruction. Engaging these receptors triggers the neutrophil to internalize foreign particles into a phagosome.
Degranulation
Degranulation involves releasing antimicrobial substances from granules. Myeloperoxidase (MPO) and elastase are enzymes stored in azurophilic granules. Upon activation, these enzymes are released into the phagosome or extracellular space. MPO produces hypochlorous acid, a potent antimicrobial, while elastase breaks down extracellular matrix components and can degrade histones during NET formation.
Neutrophil Extracellular Traps (NETs)
Neutrophil extracellular traps (NETs) are web-like structures of decondensed chromatin decorated with granular proteins that trap and neutralize pathogens. Markers of NET formation include cell-free DNA, citrullinated histone H3 (H3Cit), and granular proteins like myeloperoxidase (MPO) and neutrophil elastase (NE). These markers indicate NETosis, a distinct form of neutrophil cell death. The regulation of neutrophil lifespan and apoptosis also involves specific surface receptors, with increased expression of phosphatidylserine serving as a signal for macrophages to clear aged or apoptotic neutrophils, which contributes to inflammation resolution.
Neutrophil Markers as Indicators of Health and Disease
Neutrophil markers indicate various health conditions and diseases. For infections, particularly bacterial and fungal, increased activation markers like CD11b and CD66b signal an active immune response. Elevations in NET-related markers, such as cell-free DNA and citrullinated histone H3, are observed in severe infections like COVID-19, indicating an exacerbated inflammatory state.
Inflammation
Neutrophil markers are valuable for assessing inflammation. In sepsis, reduced neutrophil apoptosis, indicated by sustained activated neutrophils, associates with disease severity. Upregulation of markers like CD11b and CD18 on the neutrophil surface is a general sign of inflammation, facilitating their recruitment to inflamed tissues in conditions such as acute respiratory distress syndrome.
Autoimmune Diseases
In autoimmune diseases, neutrophil markers offer insights into disease activity. In rheumatoid arthritis (RA), activation markers like calprotectin and NET remnants (neutrophil elastase-DNA and histone-DNA complexes) are elevated, reflecting ongoing inflammation and potential tissue damage. These markers correlate with clinical disease activity and can predict erosive disease or joint space narrowing. In systemic lupus erythematosus (SLE), changes in neutrophil surface markers like CD31 and CD11c are observed, and “LE cells” (neutrophils engulfing immune complexes) were an early diagnostic marker.
Cancers
Neutrophil markers contribute to understanding certain cancers, such as myeloid leukemias. While AML diagnosis often involves genetic analysis of hematopoietic progenitor cells, neutrophils and their precursors play a role. Myeloperoxidase (MPO) is a cytoplasmic marker used to identify human neutrophils and differentiate acute myelogenous leukemia from acute lymphoblastic leukemia. Monitoring neutrophil-related markers can assist in tracking disease progression or treatment response, often measured via blood tests and flow cytometry.