Granular contents of Neutrophils and Platelets

Neutrophil Granules

Azurophilic (Primary) Granules

• These are lysosomes that occur in all granulocytes, as well as in lymphocytes and monocytes.
• In addition to expected lysosomal hydrolases, they also contain peroxidases (used to demonstrate azurophilic granules chemically).
• Develop earlier than specific granules.
• Stains blue/purple by Romanowsky stain.

Mnemonic: ABCDE MnOP

1. Acid hydrolase
2. BPI (Bactericidal Permeability Increasing) protein
3. Cathepsin G
4. Defensin
5. Elastase
6. Myeloperoxidase (MPO)

Specific (Secondary) Granules

• Do not stain intensely with Romanowsky stain.
• Smaller and more numerous than specific granules.

Mnemonic: COLA

1. Collagenase
2. Cathelicidin
3. Oxidase (NADPH oxidase)
4. Lactoferrin
5. Alkaline phosphatase

Common to both Azurophilic and Specific Granules

1. Lysozyme
2. Phospholipase A2 (PLP A2)

Tertiary Granules

• Cathepsin
• Gelatinase

Defect in Neutrophil Granules

1. Alpha granule defect:

Myeloperoxidase (MPO) deficiency:

• Most common neutrophil defect.
• Microbicidal activity of neutrophil is delayed but not absent (defective HOCl formation).
• Acquired form is seen in AML.

Chediak-Higashi Syndrome (CHS):

• Defect in LYST (lysosomal transport) protein, encoded by CHS1 gene at 1q42.
• Abnormal giant alpha granules, impaired chemotaxis and phagolysosome formation leading to severe bacterial infections.
• Giant granules in: melanocytes and hair (oculocutaneous albinism), nerve tissue (peripheral neuropathy).

2. Specific granule defect (SGD):

• Misnomer
• Defect of both primary and specific granules: Absent specific granules + Absent Lactoferrin and ALP (primary granules) but normal MPO.

3. NADPH oxidase deficiency: Chronic Granulomatous Disease (CGD)

• Mostly X-linked recessive trait; 30% autosomal recessive
• Infections due to catalse positive organisms (organisms that destroy their own hydrogen peroxide) – extensive inflammatory reactions, and lymph node suppuration is common despite administration of appropriate antibiotics.

Platelet Granules

Alpha granules

Mnemonic: Alpha granules are bigger like Alpha males. These are bigger molecules like proteins and peptides. The granules can be remembered using mnemonic Platelet Function Test (PFT).

1. P-selectin
2. Platelet factor 4
3. Platelet Derived Growth Factor (PDGF) and othr growth factors
4. Fibronectin
5. Fibrinogen and other factors (factor V, VIII and vWF)
6. Transforming Growth Factor – beta (TGF-beta)

Delta (Dense) granules

Mnemonic: Delta granules are smaller and weakers like Delta males. These are smaller molecules. It can be remembered using mnemonic – CAN.

1. Cations (Ca++, Mg++)
2. Amines (Serotonin, Histamine)
3. Nucleotides (ADP, ATP, PPi)

Lysosomes

Defect in Platelet Granules

Alpha granule defect:

• Gray platelet syndrome (Alpha storage pool defect) – characterized by thrombocytopenia and abnormal enlarged gray-blue platelets with a washed-out appearance due to deficeint alpha granules.
• Quebec platelet disorder – an autosomal dominant trait caused by deficient platelet alpha granule factor V (due to increased expression of alpha granule urokinase-type plasminogen activator that generates plasmin and cleaves factor V) but normal plasma factor V.

Delta granule defect:

• Delta storage pool defect – Normal number and normal appearing platelets in peripheral smear, absence of dense granules in electron microscopy and impaired second wave of platelet aggregation (prolonged bleeding time).
• Hermansky-Pudlak syndrome and Chediak-Higasghi syndrome – Rare autosomal disorders that have in common platelet dense granule deficiency, albinism and lysosomal granule defects.