EM 169 Neutrophil

Neutrophil

Neutrophils are phagocytic cells that engulf and kill microbes (especially bacteria). They have a multilobed nucleus and contain numerous granules.

• Specific Granules (purple) - smaller, round (less electron-dense) or elongated granules.
  • Antimicrobial proteins, bactericidal enzymes, and extracellular matrix degrading enzymes.
  • NADPH oxidase components needed to produce toxic oxygen radicals and hydrogen peroxide (H₂O₂).
  • Fuse with phagosomes or are secreted.
• Azurophilic Granules (black) - larger, round (electron-dense) granules. Lysosome-related organelles that contain extra proteins.
  • Antimicrobial proteins, bactericidal enzymes, and lysosomal degradative enzymes.
  • Myeloperoxidase needed to convert hydrogen peroxide (H₂O₂) into highly toxic hypochlorous acid (HOCl; similar to bleach).
  • Fuse with phagosomes (less often are secreted).
• Gelatinase Granules - look like specific granules.
  • Adhesion receptors, chemotactic receptors, and extracellular matrix degrading enzymes.
  • Secretion granules.

Although a neutrophil contains numerous granules, it contains relatively few organelles.

• Plasma Membrane (dark green) - extends small processes (pseudopodia) involved in motility and engulf microbes during phagocytosis.
  • Large number of cell surface receptors for growth, adhesion, chemotaxis, and cell-to-cell interactions.
• Nucleus (blue) / Nuclear Envelope (purple) - three to five lobes connected by thin strands of chromatin.
• Golgi Apparatus - poorly developed (not visible).
• Mitochondria (red) - small, few in number.
• Endoplasmic Reticulum (cyan) - scattered fragments.
• Glycogen (#1,#2; dark green) - numerous clusters of small granules.
• Cytoplasm (green)

Neutrophils use anaerobic glycolysis of the abundant glycogen as an energy source. Useful in the low oxygen environment of inflamed (or damaged) tissue.

Neutrophil Activation

Neutrophils are among the first immune cells to arrive at a site of infection. They leave the circulation and migrate into tissues where they phagocytose microbes and other foreign substances.

Neutrophil granules play a pivotal role in these processes.

• Gelatinase granules are secreted during movement through the walls of blood vessels (diapedesis).
  • Exposes additional adhesion and chemotactic receptors on the cell surface
  • Releases extracellular matrix degrading enzymes to digest the basal lamina.
• Limited secretion of specific granules to aid migration through tissues.
  • Exposes receptors on the cell surface that recognize microbes.
  • Releases extracellular matrix degrading enzymes.

Neutrophils are attracted by a variety of signaling molecules that bind to cell surface receptors (chemotaxis).

Intracellular Killing

Neutrophils rapidly engage, engulf, and kill microbes.

• Microbes are recognized by cell surface receptors.
• Phagocytosis of microbes into phagosomes.
• Specific and azurophilic granules fuse with phagosomes to form phagolysosomes.
• Microbes inside phagolysosomes are damaged and killed using the contents from both types of granules.
  • Antimicrobial proteins, bactericidal enzymes, serine proteases, and acid hydrolases.
  • Generation of more effective cytotoxic oxidants (i.e., respiratory burst).
    • NADPH oxidase (from specific granules) produces toxic oxygen radicals and hydrogen peroxide (H₂O₂).
    • Myeloperoxidase (from azurophilic granules) converts hydrogen peroxide to highly toxic hypochlorous acid (HOCl; similar to bleach) which is extremely antibacterial.

Neutrophils primed by some cytokines or overstimulation release specific and azurophilic granules damaging host tissues.