Neutrophils (also known as polymorphonuclear leukocytes or PMNs) are the first responders in acute inflammation and the most abundant circulating white blood cells.
| Feature |
Description |
| Life span |
1–2 days in tissue |
| Synonyms |
Segmented neutrophils, PMNs |
| Nucleus |
Multi-lobed (3–4 lobes) |
| Cytoplasmic granules |
Contain antimicrobial enzymes and peptides |
Granules and Their Contents
- Primary (Azurophilic) Granules
- Myeloperoxidase (MPO)
- Phospholipase A₂
- Lysozyme (hydrolyzes bacterial cell walls)
- Acid hydrolases
- Elastase
- Defensins (antimicrobial peptides)
- Bactericidal/permeability-increasing protein (BPI)
- Secondary (Specific) Granules
- Phospholipase A₂
- Lysozyme
- Leukocyte alkaline phosphatase (LAP)
- Collagenase
- Lactoferrin (chelates iron)
- Vitamin B₁₂ binding proteins
Clinical Correlate: Nuclear Segmentation
Neutrophil Adhesion and Migration
Steps of Neutrophil Extravasation
| Step |
Process |
Key Molecules |
| 1. Rolling |
Weak binding between neutrophils and endothelium |
Selectins (E-selectin, P-selectin) on endothelium; Sialyl Lewis X on neutrophils |
| 2. Activation |
Cytokines (IL-8, TNF, IL-1) activate neutrophils to increase integrin affinity |
Chemokines |
| 3. Firm adhesion |
Strong binding to the endothelium |
Integrins (LFA-1, MAC-1) on neutrophils bind ICAM-1/VCAM-1 |
| 4. Diapedesis (Transmigration) |
Movement through the endothelium |
PECAM-1 (CD31) |
| 5. Chemotaxis |
Migration toward the site of inflammation |
C5a, IL-8, LTB₄, bacterial N-formyl peptides |
Selectin and Integrin Distribution
| Location |
Molecule |
Function |
| Endothelium |
P-selectin, E-selectin |
Rolling |
| Leukocyte |
L-selectin |
Rolling |
| Endothelium |
ICAM-1, VCAM-1 |
Firm adhesion |
| Leukocyte |
LFA-1, MAC-1, VLA-4 |
Integrin-mediated adhesion |
| Junctions |
PECAM-1 (CD31) |
Transmigration |
Regulation of Adhesion
- Rapid response: Redistribution of pre-formed molecules (e.g., P-selectin from Weibel–Palade bodies after histamine/thrombin exposure).
- Slow response: Cytokine-induced synthesis of adhesion molecules (e.g., IL-1, TNF → ↑ E-selectin, ICAM-1, VCAM-1).
- Affinity change: Chemokines convert low-affinity integrins to → high-affinity state.
Clinical Correlates: Adhesion & Chemotaxis Defects
| Condition |
Defect |
Clinical Features |
| Leukocyte Adhesion Deficiency Type I |
Defective β₂ integrin (CD18) |
Recurrent bacterial infections, delayed umbilical cord separation |
| Diabetes mellitus, steroid use, and alcohol |
↓ adhesion molecule expression |
Impaired wound healing, infection risk |
| Chédiak–Higashi Syndrome |
Defective microtubule polymerization → impaired chemotaxis/degranulation |
Giant lysosomal granules, neutropenia, recurrent infections |
Phagocytosis and Killing Mechanisms
Oxygen-Dependent Killing (Respiratory Burst)
- Requires NADPH oxidase → produces superoxide (O₂⁻), H₂O₂, and OH· radicals.
- Myeloperoxidase (MPO) converts H₂O₂ + Cl⁻ → HOCl (bleach) = powerful microbicidal agent.
| Defect |
Mechanism |
Test |
Result |
| Chronic Granulomatous Disease (CGD) |
NADPH oxidase deficiency → no superoxide |
Nitroblue Tetrazolium (NBT) test |
Negative (yellow) |
| Myeloperoxidase Deficiency |
MPO enzyme absent |
NBT test |
Positive (purple) |
Oxygen-Independent Killing
-
Mediated by lysozyme, lactoferrin, defensins, BPI, and acid hydrolases.
Key Points to Remember
- Neutrophils are = first line of defense in acute inflammation.
- Selectins = rolling, integrins = sticking.
- PECAM-1 (CD31) = transmigration through endothelium.
- MPO + H₂O₂ + Cl⁻ → HOCl = most potent antimicrobial mechanism.
- Hypersegmented neutrophils = megaloblastic anemia.
- CGD → recurrent catalase-positive infections.
- LAD Type I → delayed cord separation + recurrent infections.
Learning Objective
By the end of this topic, the student should be able to:
- Describe the structure and granule contents of neutrophils.
- Outline the steps of neutrophil adhesion, migration, and chemotaxis.
- Distinguish between oxygen-dependent and -independent killing mechanisms.
- Recognize key disorders associated with neutrophil dysfunction (e.g., CGD, LAD, Chédiak–Higashi).
Activity:
