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ROLE OF NEUTROPHIL AND

ANTIOXIDANTS IN
PERIODONTOLOGY

DR. NIVEDITHA S
POST GRADUVATE STUDENT
DEPARTMENT OF PERIODONTOLOGY
NEUTROPHILS
A polymorphonuclear neutrophil (PMN), commonly
called polymorph or neutrophil
Size: 12-15 μm in diameter

Differential count : 50% – 70%

 multilobed nuclei: having 2-5 lobes

Fine violet pink granules

with pale cytoplasm.


First circulating cells to migrate to the site of
infection.
They form the first line of defence

Maturation PMN in the bone marrow and released into

bloodstream.
Generated continuously from bone marrow

( ~1011cells/day )
Functions of neutrophils
1. Margination and pavementing

leukocytes normally travel along the centre of the


lumen of the blood vessels ,but the inflamed tissues the
blood flow is slowed by fluid exudation and they adhere
more readily to endothelial cells, mechanism is called
margination and pavementing.
2. ROLLING AND ADHESION

 Peripherally marginated and pavemented

neutrophils slowly roll over the endothelial cells


lining the vessel wall (rolling phase). This is
followed by the transient bond between the
leucocytes and endothelial cells becoming firmer
(adhesion phase).
The following molecules bring about rolling and adhesion phases.

1. Selectins

a) P-selectin :- preformed and stored in endothelial cells and


platelets is involved in rolling,

b) E-selectin :- synthesised by cytokine activated endothelial cells


and associated with both rolling and adhesion;

c) L-selectin:- expressed on the surface of lymphocytes and


neutrophils is responsible for homing of circulating lymphocytes
to the endothelial cells in lymph .
3. EMIGRATION

The neutrophils lodged between the endothelial cells

and basement membrane cross the basement


membrane by damaging it locally with secreted
collagenases and escape out into the extravascular
space this is known as emigration.
Chemotaxis : In is the directed movement of a cell along

a chemical gradient. The neutrophils are attracted by

chemical signals from multiple sources.


KILLING AND DEGRADATION
Disposal of microorganisms can proceed by following

mechanisms.
1. Non – oxygen dependent killing mechanism.(Non –
oxidative mechanisms).

2. Oxygen dependent killing mechanism.(Oxidative


mechanisms).
Oxidative mechanisms
 Formation of phagosome.

 Increase in the activity of NADPH of phagosome

oxidase.
 Increased oxygen consumption with an increased

formation of ROS – “RESPIRATORY BURST”.


 NADPH, utilize to reduce molecular oxygen bound to

cytochrome, causing a burst of oxygen consumption.

 As a result oxygen is converted to superoxide ion,

hydrogen peroxide, singlet oxygen and hydroxyl radical,

all of which are powerful microbial agents.


Non – oxidative mechanisms
 It is mainly based on the various components of cell.

 Neutrophils contain three types of granules:

1. Primary granules: Myloperioxidases,lysoyme,acid


phosphatase and acid hydrolases.
2. Secondary granules: Lactoferrin,lysozyme.

3. Tertiary granules: Alkaline phosphtase,collagenase and


gelatinase.
 Lysozyme and lactoferrins as well as certain cationic
proteins acts as a bacteriostatic substance, which are
oxygen independent and function under anaerobic
conditions.

 Finally hydrolytic enzymes digest the killed organisms and


the degraded products are released to the exterior.
Neutrophils – mediated periodontal tissue
destruction
 Two prominent mechanisms have explained the role of
neutrophils ,
1. Impaired neutrophils
2. Hyperactive neutrophils
 Mediators produced as a part of host response that contribute
to tissue destruction include :
1. Protenases
2. Cytokines
3. Prostaglandins
 MMP-8 is released by infiltrating neutrophils,cathespsin
-G a bactericidal Protenases is responsible for activation
of MMP-8.
 Cathespsin –G is elevated in gingival tissues and GCF in
adult periodontitis.
 Elevated level of GCF are associated with active
periodontal attachment loss and elastase in GCF provide a
clinical marker for disease progression
Neutrophils Disorders Associated With
Periodontal Diseases
 Diabetes mellitus

 Pappillon –Lefevre syndrome

 Down syndrome

 Chediak – Higashi syndrome

 Drug induced agranulocytosis

 Cyclic neutropenia
Periodontal Disease Associated With
Neutrophils Disorders
 Acute necrotizing ulcerative gingivitis.(ANUG)

 Localized juvenile periodontitis.

 Pre- pubertal periodontitis.

 Rapidly progressive periodontitis.

 Refractory periodontitis.
ANTIOXIDANTS
 These protect against harmful oxidative reactions.

 Oxidation of molecules produces free radicals.

 These free radicals can cause harmful chain reactions

that are responsible for cell damage or cell death.


WHAT ARE FREE RADICALS ?
 Free radicals are chemical species that contain single
unpaired electron in an outer orbit.

Highly unstable and reactive


SOURCES OF FREE RADICALS
Internal sources External sources
 Mitochondria  Cigarette smoke

 Phagocytes  Environment pollution

 Perioxisomes  Radiation

 Inflammation and ischemia  UV light

 ozone
 The most important oxygen-containing free radicals in

many disease states are hydroxyl radical, superoxide anion

radical, hydrogen peroxide, oxygen singlet, hypochlorite,

nitric oxide.

 Free radicals can cause damage to parts of cells such as


proteins, DNA, and cell membranes by stealing their
electrons through a process called “Oxidation”.
Reactive Oxygen Species (ROS)

 The majority of free radicals that damage biological


mechanisms are oxygen-free radicals and these are known as
‘reactive oxygen species’ (ROS).

 ROS are oxygen derived small molecules produced as


intermediates in the redox reactions, such as ozone,
superoxide and hydrogen peroxide.

 ROS can be formed during UV light irradiation, by X rays,


gamma rays and also produced by neutrophils and
macrophages during inflammation
OXIDATIVE STRESS
Oxidative stress is essentially an imbalance between the
production of free radicals and the ability of the body to
counteract or detoxify their harmful effects through
neutralization by antioxidants.
Action of antioxidants
Antioxidants are capable of deactivating free radicals
before they attack human cells.
Properties of antioxidants
 Enzymatic antioxidants that works by catalyzing the
oxidation of different molecules.
 The chain breaking action.

 The substances including thiol groups that acts largely


sequestering transition metallic ions and damages Fenton
reactions.
Types of antioxidants
 Mainly hydrophilic and hydrophobic :

Antioxidant enzymes :
1. Catalase
2. Glutathione perioxidase
3. Glutathione reductase
4. Superoxide dismutase (Cu-Zn)
Natural antioxidants :
1. Provitamin - A
2. Ascorbic acid
3. Tocopherol
4. Sulphur amino acids
Role of antioxidants on periodontal disease

 Oxidative stress stays at the heart of the periodontal


damage, that happens from host-pathogen interactions.
 This stress is a result of excess ROS activity, antioxidant
deficiency or activation of redox sensitive transcription
factors and the creation of inflammatory stage.
 The oxidative stress plays important role in the pathology
of periodontitis.
 Antioxidants change the progress of oral problems such
as periodontitis, gingivitis by compromising antioxidant
capacity of crevicular fluid and plasma.
 One of the conditioning factors for gingivitis is ascorbic
acid deficiency.
 Within the periodontal pocket low redox potentional –
essential for the growth of sub gingival anaerobes.
 Antioxidants are also protective against oxidative stress.

 ROS generation in periodontal disease causes bone


resorption, increase matrix metalloprotenases activity.

 Antioxidant supplementation can reduce the incidence


and recurrence of periodontal disease.

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