The neutrophil is the most numerous type of white blood cell in the human body, making up 40 to 75% of circulating leukocytes. This specialized immune cell functions as the first responder of the innate immune system, rapidly migrating to sites of infection or tissue damage. Its primary function is to locate, engulf, and destroy invading pathogens, particularly bacteria, a process known as phagocytosis.
The Polymorphonuclear Shape
The most distinguishing structural feature of the neutrophil is its nucleus, which gives the cell its classification as a polymorphonuclear leukocyte. Unlike most other cells that possess a single, spherical nucleus, the neutrophil nucleus is segmented into two to five distinct lobes. These lobes are connected by thin strands of chromatin.
This segmented nuclear design is a mechanical adaptation that allows the cell to be highly flexible. The lobulated structure reduces the overall rigidity of the nucleus, which is typically the largest and stiffest component of a cell. This increased flexibility is necessary for the cell to perform diapedesis, the process of squeezing through tiny gaps in the blood vessel walls and navigating narrow tissue spaces to reach the infection site.
By adopting this malleable conformation, the cell can pass through constrictions as small as three micrometers in diameter without sustaining damage to its DNA. The nuclear segmentation is a structural prerequisite for the neutrophil’s ability to migrate quickly and efficiently through complex biological environments.
The Granule Arsenal
The cytoplasm of the neutrophil is packed with numerous membrane-bound vesicles called granules, which are classified into distinct subsets based on their specific protein contents. These granules serve as an arsenal of antimicrobial agents released upon cell activation.
The primary, or azurophilic, granules contain lytic enzymes and proteins designed for pathogen destruction. They are characterized by the presence of myeloperoxidase (MPO), an enzyme that produces highly reactive microbicidal compounds like hypochlorous acid. Primary granules also store neutrophil elastase and cathepsin G, which are serine proteases capable of degrading bacterial proteins and tissue components.
The secondary, or specific, granules are the most abundant in the mature cell. They contain proteins that aid in both antimicrobial defense and inflammation modulation, such as lactoferrin, which sequesters iron needed for bacterial growth. Secondary granules also house components of the NADPH oxidase complex, responsible for generating the reactive oxygen species used in the respiratory burst.
The third type, tertiary granules, are the most readily mobilized and contain matrix metalloproteinases, like gelatinase, which help the cell break down the extracellular matrix to facilitate tissue migration. The contents of these three granule types are released in a highly regulated, hierarchical manner upon cell activation.
Structural Basis for Mobility
The rapid and directed movement of the neutrophil, known as chemotaxis, relies on a highly dynamic internal scaffolding called the cytoskeleton. This structure is primarily composed of actin and myosin filaments, which undergo rapid assembly and disassembly in response to external chemical signals. The cell constantly senses its environment for chemoattractants, which are chemical cues released by pathogens or damaged tissue.
When a gradient of chemoattractant is detected, the actin filaments beneath the cell membrane begin to polymerize at the leading edge. This polymerization pushes the membrane outward, forming a broad protrusion known as a pseudopod, or “false foot,” that points toward the source of the signal.
Simultaneously, the motor protein myosin II concentrates and contracts at the cell’s trailing edge, or rear. This contraction helps retract the back of the cell and facilitates the detachment of the cell from the surface it is crawling upon. The coordinated activity between the forward-pushing actin polymerization and the rearward-pulling myosin contraction allows the neutrophil to rapidly polarize and move through tissues to confront the infection.