Learning Objective

Describe the structure, granules, functions, and clinical significance of neutrophils, including chemotaxis, morphological changes, and pathological alterations.

General Features

• Role: First responders in acute inflammation; key phagocytic cells.
• Nucleus: Multilobed (“polymorphonuclear”), usually 2–5 lobes.
• Granules:
  • Specific granules (secondary): Contain leukocyte alkaline phosphatase (LAP), collagenase, lysozyme, lactoferrin — important for extracellular pathogen killing.
  • Azurophilic granules (primary, lysosomes): Contain proteinases, acid phosphatase, myeloperoxidase, β-glucuronidase — for intracellular killing.

Neutrophil Chemotaxis

Neutrophils are recruited to sites of infection/inflammation by:

• Complement factor C5a
• Interleukin-8 (IL-8)
• Leukotriene B4 (LTB4) & 5-HETE
• Kallikrein
• Platelet-activating factor (PAF)
• N-formylmethionine peptides from bacteria

Morphological Changes in Disease

• Left shift: Presence of immature neutrophils (band cells, metamyelocytes) in peripheral blood → indicates increased myeloid proliferation, e.g., infection, inflammation, or chronic myeloid leukemia (CML).
• Toxic granulation: Dark, coarse cytoplasmic granules seen in severe infections or inflammation.
• Döhle bodies: Light blue cytoplasmic inclusions; indicative of infection or stress.
• Cytoplasmic vacuoles: Seen in severe bacterial infections.
• Leukoerythroblastic reaction: Left shift accompanied by immature RBCs; suggests bone marrow infiltration (myelofibrosis, metastasis).
• Hypersegmented neutrophils: Nucleus with ≥5–6 lobes; characteristic of vitamin B12 or folate deficiency.

Clinical Significance

• Neutrophilia: Occurs in bacterial infections, inflammation, stress, or myeloproliferative disorders.
• Morphology changes: Help distinguish acute bacterial infections, nutritional deficiencies, and marrow pathology.
• Chemotactic defects: Can lead to immunodeficiency syndromes (e.g., LAD, Chediak-Higashi).

Activity