NEUTROPHILS IN DISEASE

The tissue destruction characteristic of periodontal disease is a result of an imbalance between

the host inflammatory process and specific pathogenic bacteria residing in the periodontal
crevicular area.

One of the major players on this inflammatory and immunologic battleground is the
polymorphonuclear leukocyte (PMN) or neutrophil. Hart et al 1994, reviewed evidence placing
the neutrophil in a central host response role against invading periodontal pathogens.

Six stages of neutrophil function

1. Rolling vascular endothelium.

2. Adherence to the endothelial lining.

3. Migration (chemotaxis) toward the site of the infection.

4. Adherence to microorganisms.

5. Engulfment of bacteria (phagocytosis).

6. Intracellular killing.

Defects in any of these function or marked decrease in the number of neutrophils may result in
varying degree of susceptibility to infection. These qualitative or quantitative defects may
be inherited, acquired or drug-induced.

Decrease number of neutrophil (Neutropenia) leads to increased susceptibility to infection.

Normal range of neutrophil count 1800-8000 ul. Neutropenia is considered clinically
significantly when the absolute neutrophil count falls below 1000 cells/ul. When absolute
neutrophil count less than 500 cells/ul causes impaired control of endogenous bacteria thus
leads to series of infection complications. Less than 200 cells /ul causes inability to mount an
inflammatory response.

Neutropenia can be inherited, congenital, acquired secondary to infection malignancy, certain

medications, neutritional deficiencies or hematopoietic disease.
Pathophysiology of neutropenia classified as

a. Abnormalities of bone marrow stem cell development

b. Impaired release of neutrophils from the bone marrow
c. Abnormalities in distribution of neutrophils, between the circulating and marginating
pool in the blood.
d. Decrease survival of neutrophil in the blood (Boxer LA et al )

Diagnosis of neutropenia is based on clinical signs and symptoms as well as absolute neutrophil
counts.
Qualitative disorders of neutrophil function also increase the host’s susceptibility to infection.
Classification of neutrophil disorders corresponds with the major neutrophil processes:

1. Margination (rolling and adhesion),

2. Chemotaxis and migration,
3. Phagocytosis,
4. Degranulation and killing

1. Margination (rolling and adhesion)

Defects in the process of margination can occur at two levels. The first is a defect in a specific
neutrophil ligand called the Sialy-Lewis x protein (CD15s). A defect in this glycoprotein will
result in the loss of the neutrophil’s ability to ‘‘roll’’ along the endothelial lining of venules.
Alterations in the selectin-mediated rolling function prevent the neutrophil’s egress from the
venules. The defect is detected through flow cytometry using a commercially available
monoclonal antibody directed against the membrane surface antigens associated with CD15s.
The disease associated with this deficit is leukocyte adhesion deficiency type 2 (LAD-II).

The second neutrophil defect involving margination is at the level of neutrophil adhesion to the
endothelial cell. Defects in neutrophil surface integrins CD18/CD11a, CD18/CD11b, and
CD18/CD11c prevent the neutrophil from adhering to the endothelium. Inability to adhere to
endothelial cells prevents the migration of neutrophils to the site of infection. In addition, since
these integrins are also responsible for neutrophil adhesion to opsonized bacteria, the
neutrophil’s ability to phagocytize bacteria is compromised (Malech HL et al 1997).
Defects on CD18 and CD11 peptides are also identified by flow cytometry. Deficiency of
these intergrins is termed Leucocyte adhesion deficiency type-I (LAD-I)

2. Deficits in Neutrophil Chemotaxis and migration,

It can be either inherited, or secondary to a number of other neutrophil defects caused by a

variety of diseases or medications (Holland SM,2001). Any alteration in the neutrophil
cytoskeleton or its ability to sense or respond to a chemotactic gradient will interfere with the
cell’s ability to reach the site of infection. Neutrophil chemotactic deficits are diagnosed in
vivo through the use of the Rebuck skin window or in the laboratory using a Boyden chamber
or the agarose technique.
The Rebuck skin window measures the movement of neutrophils on a glass slide or coverslip
applied to a superficial abrasion made on the patient’s skin (Cornbleet et al,1991).

3. Primary defects in Neutrophil Phagocytosis

These defects are very rare defect. Impairment of phagocytic function is usually caused by
deficiencies in certain immunoglobulin isotypes and other opsonization factors rather than
intrinsic defects in the neutrophil (Lakshman R et al,2001). Assays of phagocytosis utilize
either inert particles (stained oil droplets, fluorescent microspheres, latex beads) or radiolabeled
microorganisms (bacteria, yeast) that are detectable within the cell after phagocytosis.
Following incubation, the ingested particles are quantified to determine if phagocytosis is
impaired.

4. Defects in Neutrophil Degranulation and killing

Defects in intracellular killing can be divided into those disorders affecting the oxidative or
non-oxidative pathways. Degranulation within the neutrophil is a non-oxidative function.
There are two main conditions with defects in degranulation – Chediak- Higashi syndrome
and specific granule deficiency.
Chediak-Higashi syndrome is characterized by fusion of cytoplasmic granules forming large
but defective granules. Degranulation is either delayed or incomplete, leading to impaired
intracellular killing. This neutrophil disorder is diagnosed with peripheral blood smears to
identify the large azurphilic cytoplasmic granules.
Specific granule deficiency manifests in the absence of secondary or specific granules. In this
disease, there is decreased availability of specific enzymes and adhesion molecules normally
present in secondary granules. Diagnosis of specific granule deficiency is through the use of
Wright stain confirming the absence of secondary granules. Assays for constituent proteins of
these granules should also demonstrate a reduction or absence compared to normally
functioning neutrophils.
The neutrophil’s oxidative killing mechanism involves two main enzymes that, in rare
instances, can be dysfunctional such enzymes are NADPH oxidase and Myeloperoxidase.
The first involves defects in the five components of the complex enzyme NADPH oxidase.
NADPH oxidase catalyzes the respiratory burst with the production of microbicidal superoxide
anion, hydrogen peroxide and hydroxyl radical. Without this oxidative reaction, bacterial
killing is greatly impaired. This neutrophil defect is responsible for the life threatening
recurrent infections found in chronic granulomatous disease.

Diagnostic tests for oxidative metabolism include the nitroblue tetrazolium test. In this test,
neutrophils are stimulated and incubated with the colorless nitroblue tetrazolium. If NADPH
oxidase is functioning, the nitroblue tetrazolium is reduced, leaving a blue black formazan
precipitate. If the oxidative burst is defective, no precipitate is formed. A more sensitive test to
measure the respiratory burst involves flow cytometry. Hydrogen peroxide converts
dihydrorhodamine to rhodamine and this is detected using a florescent label.

Another deficiency in the oxidative pathway is the absence of myeloperoxidase. A deficit of

this enzyme will lead to a lack of hypochlorous acid and a delay in bacterial killing.
Myeloperoxidase deficiency is diagnosed using peroxidase staining of blood films, flow
cytometry or direct assay of enzyme activity.

There are numerous diseases related to deficiencies in both neutrophil number and function,
only a few have been specifically related to periodontal disease in the medical and dental
literature. The following conditions were systemic conditions with neutrophil dysfunction in
which periodontal disease manifested as oral manifestations.
Systemic disease Neutrophil deficit Clinical manifestations

Chediak-Hagashi Syndrome Altered migration, Aggressive periodontitis,oral

Degranulation, ulceration,
phagocytosis oculocutaneous albinism ,
recurrent infections, bleeding
tendencies

Chronic granulomatous Defective NADPH oxidase Recurrent bacterial and

disease with impaired intracellular fungal infections,
killing lymphadentitis; skin
abscesses,
gingivitis/periodontitis.

Cyclic neutropenia Decrease (cyclic)in Periodic fever, malaise, oral

production and release of ulcers;
neutrophils gingivitis/periodontitis

Leukocyte adhesion Impaired adherence to Delayed umbilical core

deficiency (type 1) vascular separation,persistent
endothelium,impaired infections in absence of
phagocytosis purulence, severe
periodontitis, fiery-red
mucosa

Leukocyte adhesion Impaired rolling along Short stature, mental

deficiency (type 2) vascular endothelium retardation, recurrent
infections, skeletal
abnormalities, likely
periodontitis.
Systemic disease Neutrophil deficit Clinical manifestations

Papillon-LeFe`vre syndrome Variable-deficits in Palmoplantar hyperkeratosis,

chemotaxis,phagocytosis severe aggressive
periodontitis, premature
tooth loss

Lazy leukocyte syndrome Neutropenia,depressed Recurrent infections, fever,

chemotaxis cough, oral ulcers, skin
abscesses, gingivitis,
periodontitis.

Familial benign chronic Decrease (noncyclic)in Recurrent oral ulcers, otitis

neutropenia absolute number of media, upper respiratory
neutrophils tract infections, hyperplastic,
edematous, fiery-red
gingival tissues.

Agranulocytosis Neutropenia Fever,necrotizing

gangrenous lesions without
purulence,oral
ulcers,spontaneous
bleeding,periodontitis.
Neutrophil function in periodontitis

Comparison of neutrophil functions in aggressive and chronic periodontitis

The earliest pioneering work on neutrophil functions and periodontal diseases in general and
aggressive periodontitis in particular indicated an impairment of neutrophil functions
responsible for host protection.
For the next decade, the prevailing view was that impaired neutrophil functions, as well as
impaired functions of other cells of the host response, were a central mechanism in the
progression of chronic and aggressive forms of periodontitis.
However, in subsequent decades, the concept of a “primed” or hyperactive neutrophil,
particularly in aggressive periodontitis, began to emerge (21, 29, 43, 56), leading to a new
perspective on the role of neutrophils in aggressive periodontitis, as well as the destructive role
of inflammatory cytokines from the cell-mediated response.

In the absence of a specific stimulus such as microbial colonization in the gingival crevice ⁄
periodontal pocket, neutrophils flow within the terminal circulation system in the periodontal
tissue, with a proportion of these neutrophils rolling along the endothelial lining. This rolling
motion along the endothelial lining is facilitated through weaker binding of selectins on the
neutrophil surface to lectins on the endothelial lining.

Neutrophils respond to binding of microbial products or antigens resulting from microbial

colonization of the tooth surface, such as the small bacterial chemotactic peptide N formyl
methionyl- leucyl-phenylalanine.

One of the first responses to such binding is shedding of the selectins on the neutrophil surface,
with a concomitant increased expression of integrins of the CD11 ⁄ CD18 (cluster determinant
11 ⁄ 18) family on the neutrophil cell surface.
These integrins enable the neutrophil to adhere more tightly to intercellular adhesion molecules
on the surface of endothelial cells, and facilitate migration of neutrophils through the
endothelial lining and into the lamina propria of the periodontal tissues. The actual movement
of neutrophils into the tissue is driven by an actin filament motor through polymerization and
depolymerization of intracellular actin filaments. Neutrophils then move out of the lamina
propria into the gingival crevice ⁄ periodontal pocket, where they attempt to engulf ⁄
phagocytose and kill the bacteria on the tooth surface.
This process of engulfing the bacteria via phagocytosis and eliminating them by intracellular
killing is facilitated by two neutrophil processes:
(i) Release of enzymes such as myeloperoxidase and a variety of proteolytic enzymes
from lysosomal granules, and
(ii) The oxidative burst, which entails the synthesis and release of superoxide and
hydroxyl radicals, and subsequent conversion of these products to hydrogen
peroxide.
Neutrophils secrete other bactericidal substances such as calprotectins and cathelicidins as part
of the innate immune system.

Both impaired neutrophils and primed ⁄ hyperactive neutrophils may play a role in the
pathogenesis of aggressive and chronic periodontitis.

The impaired neutrophil model in aggressive periodontitis

Regarding neutrophil count a reduced number of neutrophils or proportion of neutrophils in
the whole leukocyte population that may in turn impair the host response to the subgingival
microbiota.
There is clear evidence that patients who have low counts of circulating neutrophils due to rare
conditions such as cyclic neutropenia present with a pattern and progression of loss of
periodontal attachment that is similar to that of aggressive forms of periodontitis (Genco RJ).
However, low neutrophil counts have not been demonstrated in either chronic or aggressive
forms of periodontitis (Buchmann R et al,Hidalgo et al). Hidalgo et al demonstrated elevated
neutrophil counts in patients with generalized aggressive periodontitis. Buchmann et al found
that the numbers and proportions of neutrophils in serum are similar in aggressive and chronic
forms of periodontitis.Thus the relevance of neutrophil counts in aggressive periodontal
diseases remains unresolved.
Impairment of neutrophil function centered on impaired chemotaxis in response to signals
from bacterially derived f- Met-Leu-Phe peptides.
Reduced neutrophil chemotaxis in aggressive periodontitis patients was observed in vivo using
an external skin window test without f-Met-Leu-Phe stimulation, and this pattern of chemotaxis
was unaltered on addition of f-Met-Leu-Phe (Palmer et al). By contrast, in studies that
compared neutrophil chemotaxis in chronic and aggressive periodontitis patients, the patients
in the chronic periodontitis group exhibited either a normal or elevated chemotaxis response
(Altman LC et al,Takahashi et al).

Impaired chemotaxis in aggressive but not in chronic forms of periodontitis, the consensus is
that the chemotaxis defect may involve faulty surface receptors for chemotactic stimulants.
This could be due to
(i) A reduction in the number of receptors on the neutrophil cell membrane,
(ii) An inherent or acquired defect in the f-Met-Leu-Phe membrane receptor itself and
⁄ or coreceptors for the f-Met-Leu-Phe receptor such as GP110 (glycoprotein 110)
or CD38 that facilitate and enhance the chemotatic response (Van Dyke TE et al )
(iii) A combination of both.

Early indications supported a decrease in the number of neutrophil receptors for both f-Met-
Leu-Phe and the GP110 co-receptor.
Fuji et al in their studies there was a significant decrease of CD38 expression in f-Met-Leu-
Phe-stimulated neutrophils in localized aggressive periodontitis patients compared to normal
individuals.
However, these membrane receptor defects do not appear to influence the function of the
“motor”of neutrophil motility, the actin cytoskeleton,as the patterns of actin polymerization
and depolymerisation were normal.
In addition to impaired chemotaxis, some early studies demonstrated impaired phagocytosis
and killing in patients with localized or generalized aggressive periodontitis compared to
individuals with chronic periodontits.
Kimura et al studies showed that consistently lower percentages of neutrophils with
phagocytosed particles and lower numbers of phagocytosed particles per neutrophil in localized
aggressive periodontitis and generalized aggressive periodontitis compared to chronic
periodontitis patients.
This reduced function had not altered after treatment, implying an inherent defect that is not
affected by changes in serum factors that could be altered after periodontal treatment.
In the innate immune system, neutrophils are an important source of potent broad-spectrum
antimicrobials such as defensins and LL-37 cathelicidin.

In gingival crevicular fluid from some patients with aggressive periodontitis, LL-37
cathelicidin was reduced or absent, and there were lower levels of human neutrophil peptide
1–3 defensin compared to gingival crevicular fluid and neutrophils obtained from patients with
chronic periodontitis.
However,Fleming TF et al studies demonstrated that the reduction in these defensins was
considered to be minor and not to have a significant impact on the pathogenesis of aggressive
periodontal diseases.
A third area of study of neutrophil function that has involves possible alterations in the initial
adhesion of neutrophils to endothelial cells of capillaries. When stimulation started, this
process involves both shedding of selectins, and increased cell surface expression of CD11 ⁄ 18
integrins, which promote firmer adherence and fixation of the neutrophil to the endothelial
lining and subsequent chemotactic migration into the tissue.
Hurttia HM et al,1998 shown that unstimulated and f-Met-Leu-Phe-stimulated neutrophils
from localized aggressive periodontitis patients demonstrated higher adhesion to culture plates
than did periodontally healthy controls. But Mouynet P et al 1994,Palmer et al 1990 shown that
CD18 ⁄ CD11a and CD18 ⁄ CD11b expression on peripheral and crevicular fluid neutrophils in
localized aggressive and chronic periodontitis patients demonstrated no marked differences in
expression nor a deficiency of these adhesion integrins.

In addition to the f-Met-Leu-Phe receptor, polymorphisms in the neutrophil membrane receptor

for the Fc gamma fragment of antibody may play a role in defective phagocytosis in aggressive
periodontitis. Polymorphisms in the Fc gamma receptor occurred at a significantly higher rate
in neutrophils from patients with aggressive periodontitis vs those of periodontally healthy
controls (Kaneko S et al,2004 and Nibali L et al 2006)

Emergence of the concept of a hyperactive or primed neutrophil.

Most data have supported the concept of a hyperactive ⁄ primed neutrophil that leads to
increased tissue destruction in aggressive forms of periodontitis (Kantarci et al ).
Such priming could involve
1. Increased neutrophil adhesion,
2. Increased enzyme release and, perhaps most importantly,
3. An elevated oxidative burst.

Although expression of f-Met-Leu-Phe receptors is impaired, appears that integrin-mediated

cell adhesion may be enhanced in patients with either aggressive or chronic periodontitis
(Hurttia et al 1998).

For increased enzyme activity is supported by studies of neutrophils from patients with
aggressive forms of periodontitis who have increased intracellular levels of beta-glucuronidase,
an enzyme characteristic of azurophil lysosomes.
Patients with generalized aggressive periodontitis had greater beta-glucuronidase activity in
crevicular fluid than individuals with localized aggressive periodontitis, whose levels were in
turn greater than found in periodontally healthy controls. These higher levels of beta-
glucuronidase could lead to increased periodontal breakdown in aggressive periodontal
diseases (Albandar JM et al 1998).
Myeloperoxidase is another enzyme secreted by neutrophils that may play a central role in the
activation of neutrophil proteases In patients with aggressive periodontitis, baseline levels of
myeloperoxidase were highly correlated with the presence of bleeding and suppurating sites,
although no specific comparisons were made between aggressive and chronic periodontitis
patients (Kaner D et al ,2006).

Neutrophil-derived matrix metalloproteinases such as MMP-8 found no difference in tissue or

crevicular fluid levels of this enzyme between chronic and aggressive periodontitis patients
(Tervahartiala T et al,2000). In addition, the levels of MMP-25 and MMP-26, two newly
identified neutrophil matrix metalloproteinases involved in extracellular matrix breakdown and
turnover, were comparable between aggressive and chronic periodontitis patients (Emingil G
et al,2006).

Neutrophil priming or hyperactivity is an increase in the synthesis and release of oxidative

burst products, such as superoxide, hydroxyl radicals and hydrogen peroxide, from both resting
and stimulated cells. As in other neutrophil function studies in aggressive and ⁄ or chronic
periodontitis, there is no clear consensus as to whether the oxidative burst is increased,
decreased or unchanged in unstimulated, stimulated or both unstimulated and stimulated
neutrophils than in individual patients

Neutrophil priming by inflammatory cytokines in serum has also been implicated in aggressive
periodontitis. In one study, increased interleukin-8 plasma levels in aggressive periodontitis
patients were correlated with increased production of hydrogen peroxide by neutrophils, and
decreased L-selectin shedding, implicating interleukin- 8 in serum as a priming factor for the
neutrophil oxidative burst (Gainet J et al ,1999).

Another study found that an increase in expression of genes associated with NADPH
oxidase,which is responsible for the synthesis of oxidative burst products in both chronic and
aggressive forms of periodontitis (Nibali L et al,2006). The authors speculated that this may
also be an explanation for the altered neutrophil response that is characteristic of aggressive
periodontitis.

Defective or primed neutrophils: insights from intracellular signalling

There are several pathways, substances or nodes in the intracellular scheme that could be
investigated, but this review focuses on the three pathways and nodes that have received the
most attention:
i. Calcium homeostasis,
ii. The phosphorylation of proteins by protein kinase C, and
iii. The central role of diacylglycerol and diacylglycerol kinase.
Calcium homeostasis and alterations of intracellular pH play a critical role in a variety of
neutrophil functions, including the chemotactic response, cell motility in migration and
phagocytosis, and selected intracellular signaling pathways. Several studies have demonstrated
impairment of the initial intracellular release of calcium and the influx of extracellular calcium
into the neutrophil. Although some studies have demonstrated that the release of intracellular
sequestered calcium in the early phase of the calcium response appears to be intact in
neutrophils from localized aggressive periodontal patients (Daniel MA et al,1993), the second
phase of the calcium response, associated with membrane channel activation and influx of
extracellular calcium, appears to be compromised (Daniel MA et al,1993).
However, redistribution of the rapidly released calcium and alkalinization of the cytoplasm was
impaired in the neutrophils from aggressive periodontitis patients compared to healthy controls
(Herrmann JM et al,2005).
Calcium influx is a newly described calcium influx factor (Shibata K et al,2000). This calcium
influx factor is hypothesized to be a second messenger for the opening of membrane calcium
channels when intracellular calcium stores are depleted. The activity of this calcium influx
factor is decreased in localized aggressive periodontitis patients compared to patients with
chronic periodontitis or healthy controls.
Alterations in protein kinase C One study reported that the total calcium-dependent protein
kinase C activity of neutrophils from patients with localized aggressive periodontitis and
decreased chemotactic migration to a F-Met-Leu-Phe gradient was lower than in neutrophils
from healthy controls.
Diacylglycerol (DAG) may play a central role in this intracellular signaling process, and the
reported alterations in DAG kinase levels in neutrophils from aggressive periodontitis patients
may have a variety of effects.
Because DAG is an endogenous activator of protein kinase C, increased and prolonged
generation of DAG could lead to an abnormal pattern of protein kinase C-regulated neutrophil
functions, explaining the parallel hypo and hyperactivities (Leino L et al, 1999).
DAG is converted to phosphatidic acid by DAG kinase. Thus reduced DAG kinase levels imply
increases in intracellular DAG levels and subsequent neutrophil priming (Gronert K et al,
2004).
This role for DAG in intracellular signalling in neutrophils from aggressive periodontitis
patients is supported by studies demonstrating that the DAG levels increased by 67 and 111%
from the basal level following stimulation with f-Met-Leu-Phe

Implications for diagnosis and Treatment

Early studies suggested that a reduction of GP110 and f-Met-Leu-Phe receptors on neutrophils
is specific to localized aggressive periodontitis patients who exhibit neutrophil chemotaxis
abnormalities, and may be a useful disease marker for localized aggressive periodontitis (Van
Dyke TE et al,1987). DeNardin E et al 1990 demonstrated that some patients with aggressive
periodontitis exhibit normal chemotaxis, this approach may have limitations in diagnosing
aggressive periodontitis.

Changes in neutrophil function in aggressive periodontitis compared to chronic periodontitis

are primarily due to a defect in neutrophil functions or a priming ⁄ hyperactive effect, and
whether these changes are primarily due to inherent alterations or acquired as a result of
inflammatory or microbial challenges. The answers to these questions may influence treatment
approaches for aggressive and chronic forms of periodontitis

Kimura S et al, 1992 study that demonstrated impaired phagocytosis in localized aggressive
periodontitis patients, this reduced function was not changed after treatment, implying an
inherent defect that is not affected by serum.
On the other hand, neutrophil myeloperoxidase levels were decreased in a study on the
treatment of 23 patients with generalized aggressive periodontitis, and were related to reduction
of probing depth (Kaner et al , 2006).

In a recent series of studies on the treatment of patients with aggressive or chronic periodontitis
involving combinations of scaling and root planing, surgery if needed, and amoxicillin 500 mg
three times daily and metronidazole 250 mg three times daily for 7 days, there were reductions
of markers of neutrophil-mediated inflammation such as the enzymes cathepsin D,
myeloperoxidase and beta-glucuronidase in the gingival crevicular fluid in both the aggressive
and chronic periodontitis patients, with greater reductions after surgery. However, the levels
remained higher in the aggressive periodontitis patients (Buchmann R et al.2002).
Low-dose systemic antibiotics of the tetracycline family, such as doxycycline, can inhibit the
activities of some of the proteolytic enzymes released by neutrophils, and can act as scavengers
for products of the oxidative burst. Thus several investigators have suggested the use of low-
dose systemic doxycyclines specifically for the treatment of periodontal diseases (Lee HM et
al,2004), particularly aggressive periodontitis.

More recently, new insights into the role of products of the arachidonic acid pathway have
revealed that, in addition to proinflammatory and tissue-destructive products, such as
prostaglandins and leukotrienes, there are other products that may have anti-inflammatory ⁄
tissue protective effects (V an Dyke TE et al,2008)

These include a variety of arachidonic acid-derived lipoxins, such as lipoxin A4, which is
generated from the interaction of platelets and neutrophils, and an aspirin-generated lipoxin. In
addition, several investigators have identified metabolic modifications of omega-3 fatty acids
called resolvins that have similar structure and activity to these anti-inflammatory lipoxins. In
initial animal studies, administration of metabolically stable analogs of lipoxins and aspirin-
stimulated lipoxins inhibited migration of neutrophils in a mouse dorsal pouch model incubated
with P. gingivalis (Kantarci A et al,2005).These results also identified the neutrophil as a source
of prostaglandins, which are a potent mediator of bone resorption

However, in a human study, neutrophils from individuals with localizeaggressive periodontitis

did not respond to molecules of the lipoxin series, but Resolvin E1 did inhibit superoxide
generation (Hasturk H et al,2006)

Conclusion

Defective neutrophil functions, such as chemotaxis, phagocytosis and intracellular killing of

microbial pathogens, or primed neutrophils with elevated functions (e.g. increased oxidative
burst and destructive enzyme release) are the predominant contributor to progression of
aggressive and chronic forms of periodontitis is still open to debate. In an understanding of
neutrophil function can aid in the development of new diagnostic and treatment approaches.