This document discusses the role of neutrophils in aggressive and chronic periodontitis. It notes that a significant shift in understanding the pathogenesis of these conditions centers on alterations in neutrophil function, including impaired neutrophil function, primed/hyperactive neutrophils, and concepts under transformation. While functional alterations have been extensively studied, whether neutrophils are inherently defective or progressively damaged remains open to debate. Modulation of the destructive aspects of the host response, such as through low-dose doxycycline or anti-inflammatory lipoxins, shows promise as a treatment approach. Understanding neutrophil function could aid in developing new diagnostic and treatment strategies, with potential to reverse acquired neutrophil defects through mechanical debridement and strategic use of anti

1. DR. BHARGAVI. V
P.G II YR
DEPARTMENT OF PERIODONTOLOGY
NARAYANA DENTAL COLLEGE
NELLORE
GUIDED BY
VIJAY .K. CHAVA
PROFESSOR & HOD
OR

2. NEUTROPHIL: Predominant Polymorpohonuclear (PMN) leukocyte.
4000-8000 cells/mm3
Pale cytoplasm
Granules
Multi –lobular
nucleus
2-5 days
“Killer
machine”
Infection
InjuryRepair

3. STRUCTURE:

4. ROLE IN AGGRESSIVE & CHRONIC PERIODONTITIS:

5. Significant “paradigm shift”
in understanding the
pathogenesis of aggressive &chronic
periodontitis is centered on
ALTERATION IN
NEUTROPHIL
FUNCTION
External
factors
Inherent
changes

6. “Impairment of neutrophil function”
Cianciola LJ, Clark .RA 1977,
Vandyke TE1980,
“Primed/hyperactive neutrophil” (Destructive aspects)
Gustafson AB1997, Karima. M 2005
Matthews JB 2007007
EARLIER
EMERGING CONCEPT
New avenues of research
CONCEPTS UNDER TRANSFORMATION

7. PRIME FUNCTIONS OF NEUTROPHILS

8. IN ABSENCE OF
SPECIFIC STIMULUS
ROLLING
ADHESION
MICROBIAL PRODUCTS
& INFLAMMATORY
MEDIATORS

9. Trans Endothelial Migration
Under the influence of
chemokines
CHEMOTAXIS

10. PHAGOCYTOSIS
Oxidative
Burst
Bactericidal
substances
Enzymes

12. ADHERENCE
(CONTRADICTORY)
Higher adherence
(invitro) both stimulated
and unstimulated
PMNs in LAP
(Hurttia . H 1998)
No differences/deficiency
in integrins
(Watanabe K 1987,
Mouynet P 1995)
Adhesion
molecules-
comparable to
healthy group
(Pietruska M 2005)
1)

13. FAULTY RECEPTORS
Reduction in number
Vandyke TE 1990
Inherent/Acquired defect
In
Receptors & Co-receptors
to f-met-leu-phe
(Fujitha T 2005)
2)
IL-1R
IL-8R
CD11a-CD18
LFA-1
CD11b-CD18
Mac-1
CD45
LSPR
mCD14
f MLPR
FcR
CR3
CD44
C3aR
C5aR
Impaired
chemotaxis

14. [f- met- leu- phe, LeukotrieneB 4]
Vandyke TE 1982,
Page RC 1985,
Palmer GD 1993
Crevicular PMNs
Aggressive periodontitis
Peripheral PMNs
Reduced
Shapira L 1994
Shibata K 2000
Chronic periodontitis
Normal/elevated response
Altman LC 1985,
Takahashi K 2001
3)

15. low % of neutrophils
with phagocytosed
particles
Unaltered by changes in
serum factors after RX
Inherent defect
Kimura 1992
Phagocytes ingested
more bacteria invitro
than GAP
Eick S 2000
Impaired in LAP &GAP ptsIncreased in Healthy individuals
PHAGOCYTOSIS
Antimicrobials
(Defensins &Cathelicidins)
reduced/absent in GCF &
PMNs of AP pts.
Puklo M 2008
Minor- no significant impact
on pathogenesis
Flemming TF 1994

16. Impaired neutrophil model— Could not fully explain the possible role of PMNs
in aggressive periodontitis
Negative Evidences:
No significant
correlation
between
chemotaxis and
severity 0f
Periodontitis
Chinwalla J 1998
kinane DF 1989
Elevated
chemotatic
response
Clark RA 1977
Karima M 2005
Normal random
migration
&chemotaxis
Mouynet P 1994No difference
in chemotaxis,
phagocytosis,
Superoxide
production or
adhesion
Takahashi K 2001

18. Increased adhesion
Increased enzymatic
release
Elevated oxidative Burst
O2 -,H2O2,OH -
Priming
Increased tissue
destruction
β- Glucurodinase
Albandar JM 1998
Myeloperoxidase
Weiss SJ 1989
No difference in MMPs
Tervahartiala T 200o
Emingil G 2006
Johnstone 2007
Leino,shapira 1994
Mouynet P 1994
More in CP pts than AP on
exposure to Aa, Pg
Guentsch A 2009
Hurttia H
1998

19. PRIMING
ACQUIRED
Neutrophil priming substance in
serum
f-met-leu -phe, Pg- Shapira. L 1994
A a - Ashkenazi .M,
IL-8 – Gainet. J 1999
INHERENT DEFECT
Alterations in Genes for TNF- Alpha
kubota TT,
NADPH oxidase
Nibali 2006

21. G-protein
Phospholipase
C
3)Diacyl glycerol (DAG) calcium
1)calcium
1) Intracellular
stores of ca+22) Protein kinase C
Phosphorylation of selected proteins
Stimulation or inhibition of PMN function
agonist
Receptor
Kantarci AK 2003
Bi layered cell membrane

22. DIAGNOSIS

23. Diagnosis of AP based on clinical signs alone is challenging proposition
Lab based assessment of
Neutrophil function,
Cellular & humoral response or
Microbial parameters
might improve accuracy of
diagnosis of AP vs CP..!!

24. TREATMENT APPROACHES

25. Influenced by alteration in function
IF INHERENT
Periodontal treatment like
reducing microbial load & local
inflammatory response
Did not alter the function --- kimura S 1992
ACQUIRED
Decreased myeloperoxidase
after Rx related to decreased
probing depths
Kaner D 2006

26. TREATMENT BY MODULATION OF DESTRUCTIVE ASPECTS OF
HOST RESPONSE— “PROMISING APPROACH”

27. 1) LOW DOSE SYSTEMIC DOXYCYCLIN- Lee HM 2004
Inhibit some proteolytic enzymes and
Scanvenges products of oxidative burst
2) ARACHIDONIC ACID DERIVED ANTI INFLAMMATORY LIPOXINS:
Lipoxin A4 & aspirin derived lipoxins, Resolvins
ANIMAL STUDIES :
Inhibited neutrophil migration to Pg in vitro
kantarci A 2005.
HUMAN STUDIES:
Did Not respond to lipoxins, but resolvins inhibited superoxide generation.
Pouliot M 2000

28. SUMMARY AND FUTURE DIRECTIONS

29. Though functional alterations are--extensively studied,
Defective PMN Still open to debate
or progressive and chronic forms of periodontitis.
primed PMNs
PMN
Components
of acquired
immunity
cytokines
Pathogenisis
of
periodontitis

30. Despite these complexities ,
Understanding of neutrophil function
Development of new diagnostic and treatment approaches.
POTENTIAL TO REVERSE ACQUIRED NEUTROPHIL DEFECTS BY
a) Basic mechanical debridement
b) Strategic therapeutic use of new cost-effective approaches of treatment
anti-inflammatory agents

31. THANK YOU