What are neutrophils?

Neutrophils: The First Line of Defense in Immune Response

Neutrophils are the most abundant type of white blood cells in circulation, serving as the first line of defense in the innate immune system against infections, particularly bacterial and fungal pathogens.

Definition and Classification

• Neutrophils are defined by an absolute neutrophil count (ANC) in the blood, with normal values above 1500 cells/mm³ 1
• Neutropenia (low neutrophil count) is classified as:
  • Mild: ANC 1000-1500 cells/mm³
  • Moderate: ANC 500-1000 cells/mm³
  • Severe: ANC < 500 cells/mm³ 1

Biological Characteristics

• Neutrophils are the most abundant granulocytes and play a significant role in inflammatory reactions 2
• They are generally the first and most lethal effector cells recruited to an inflammation site 2
• Neutrophils are critical for providing host defense against infection, particularly bacterial and fungal infections 2

Neutrophil Functions

Neutrophils employ several mechanisms to eliminate pathogens:

1. Phagocytosis: Engulfing and intracellularly degrading pathogens 3
2. Oxidative burst: Rapid production of reactive oxygen species (ROS) that destroy foreign entities 2
3. Degranulation: Release of proteases and antimicrobial compounds 4
4. Neutrophil Extracellular Traps (NETs): Formation of DNA-based structures that trap and kill pathogens 3
5. Immune modulation: Interaction with dendritic cells and lymphocytes to regulate adaptive immunity 4

Clinical Significance

Infection Risk Related to Neutrophil Counts

• Risk of infection increases with the depth and duration of neutropenia 2
• Significant infection risk occurs when ANC falls below 500 cells/mm³, with highest risk below 100 cells/mm³ 1
• Fever can be an important indicator and often the only sign of infection in neutropenic patients 2
• Primary sites of infection in neutropenic patients include the alimentary tract, sinuses, lungs, and skin 1

Neutropenia Management

• Prompt antibiotic therapy is essential in febrile neutropenia 1
• Granulocyte-colony stimulating factor (G-CSF) may be used to reduce the risk of serious infections in certain clinical scenarios 1
• Prevention of infection is critical in neutropenic patients, particularly those with prolonged neutropenia after chemotherapy or stem cell transplantation 2

Emerging Concepts in Neutrophil Biology

• Neutrophil heterogeneity: Rather than being a homogeneous population, neutrophils display phenotypic and functional diversity 3
• Tumor-associated neutrophils: Can be classified into anti-tumor (N1) and pro-tumor (N2) subpopulations 5
• Immune regulation: Neutrophils are now recognized as important modulators of both inflammation and immune responses, not just simple phagocytes 3

Clinical Pitfalls

• The clinical presentation of infection in neutropenic patients may be muted due to lack of neutrophils, with fever often being the only sign 1
• Common errors in neutrophil-related conditions include delaying antibiotic therapy in febrile neutropenia and failing to recognize drug-induced neutropenia 1
• Neutrophil function can be impaired by various factors, including volatile anesthetics, which may decrease neutrophil adhesion and reactive oxygen species production 2

Understanding neutrophil biology and function is crucial for managing conditions associated with neutropenia or neutrophil dysfunction, particularly in patients with cancer undergoing chemotherapy or stem cell transplantation.