CHAPTER  14 

Gingival Inflammation
Joseph P. Fiorellini, David M. Kim, and Panagiota G. Stathopoulou

CHAPTER OUTLINE
Stage I Gingival Inflammation: The Initial Lesion
Stage II Gingival Inflammation: The Early Lesion
Stage III Gingival Inflammation: The Established Lesion
Stage IV Gingival Inflammation: The Advanced Lesion

The pathologic changes of gingivitis are associated with the pres-

ence of oral microorganisms attached to the tooth and perhaps in
or near the gingival sulcus.
These organisms are capable of synthesizing products (e.g.,
collagenase, hyaluronidase, protease, chondroitin sulfatase, endo-
toxin) that cause damage to epithelial and connective tissue cells
as well as to intercellular constituents such as collagen, ground
substance, and glycocalyx (cell coat). The resultant widening
of the spaces between the junctional epithelial cells during early
gingivitis may permit injurious agents derived from bacteria or
bacteria themselves to gain access to the connective tissue.10,44,48
Microbial products activate monocytes and macrophages to
produce vasoactive substances such as prostaglandin E2, inter-
feron, tumor necrosis factor, and interleukin-1.25,38 In addition,
interleukin-1β alters the properties of gingival fibroblasts by delay-
ing their death via mechanism-blocking apoptosis. This stabilizes
the gingival fibroblast population during inflammation.54
Morphologic and functional changes in the gingiva during
plaque accumulation have been thoroughly investigated, especially
in beagle dogs and humans.36 A useful framework for the organiza-
tion and consideration of these data has been devised on the basis
of histopathologic, radiographic, and ultrastructural features and
biochemical measurements.37,39 The sequence of events that culmi-
nates in clinically apparent gingivitis is categorized as the initial,
early, and established stages of disease, with periodontitis desig-
nated as the advanced stage38 (Table 14-1). One stage evolves into
the next, with no clear-cut dividing lines.
Despite extensive research, we still cannot distinguish defini-
tively between normal gingival tissue and the initial stage of gin-
givitis.36 Most biopsies of clinically normal human gingiva contain
inflammatory cells; these consist predominantly of T cells, with
very few B cells or plasma cells.36,49,50 These cells do not create
tissue damage, but they appear to be important in the day-to-day
host response to bacteria and other substances to which the gingiva
is exposed.36 Therefore, under normal conditions, a constant stream
of neutrophils is migrating from the vessels of the gingival plexus
through the junctional epithelium, to the gingival margin, and into
the gingival sulcus and the oral cavity.43
Stage I Gingival Inflammation:
The Initial Lesion
The first manifestations of gingival inflammation are vascular
changes that consist of dilated capillaries and increased blood flow.
These initial inflammatory changes occur in response to the micro-
bial activation of resident leukocytes and the subsequent stimula-
tion of endothelial cells. Clinically, this initial response of the
gingiva to bacterial plaque (i.e., subclinical gingivitis26) is not
apparent.
Microscopically, some classic features of acute inflammation can be
seen in the connective tissue beneath the junctional epithelium.
Changes in blood vessel morphologic features (e.g., the widening of
small capillaries or venules) and the adherence of neutrophils to
vessel walls (margination) occur within 1 week and sometimes as
early as 2 days after plaque has been allowed to accumulate18,41
(Figure 14-1). Leukocytes—mainly polymorphonuclear neutrophils
(PMNs)—leave the capillaries by migrating through the walls via
diapedesis and emigration25,50,51 (Figure 14-2). They can be seen in
increased quantities in the connective tissue, the junctional epithe-
lium, and the gingival sulcus2,3,24,34,41,45,46 (Figures 14-3 and 14-4). The
exudation of fluid from the gingival sulcus18 and extravascular pro-
teins are present.20,21
However, these findings are not accompanied by manifestations
of tissue damage that are perceptible at the light microscopic or
ultrastructural level; they do not form an infiltrate, and their pres-
ence is not considered to indicate pathologic change.36
Subtle changes can also be detected in the junctional epithelium
and the perivascular connective tissue at this early stage. For
example, the perivascular connective tissue matrix becomes
altered, and there is exudation and deposition of fibrin in the
affected area.36 In addition, lymphocytes soon begin to accumulate
(see Figure 14-2, D). The increase in the migration of leukocytes
and their accumulation within the gingival sulcus may be corre-
lated with an increase in the flow of gingival fluid into the sulcus.4

219
Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
220 PART 1  Biologic Basis of Periodontology

TABLE 14-1  Stages of Gingivitis

Time Junctional and Predominant
Stage (Days) Blood Vessels Sulcular Epithelia Immune Cells Collagen Clinical Findings
I. Initial lesion 2 to 4 Vascular dilation Infiltration by PMNs PMNs Perivascular loss Gingival fluid flow
Vasculitis
II. Early lesion 4 to 7 Vascular proliferation Same as stage I Lymphocytes Increased loss Erythema
Rete pegs around infiltrate Bleeding on probing
Atrophic areas
III. Established 14 to 21 Same as stage II, Same as stage II but Plasma cells Continued loss Changes in color, size,
lesion plus blood stasis more advanced texture, and so on

PMNs, Polymorphonuclear leukocytes (neutrophils).

Microscopic examination of the gingiva reveals leukocyte infiltration

in the connective tissue beneath the junctional epithelium, which
consists mainly of lymphocytes (75%, with the majority being T
OSE JE cells)41,47 but that also includes some migrating neutrophils as well
as macrophages, plasma cells, and mast cells. All of the changes
seen in the initial lesion continue to intensify with the early
lesion.15,28,30,35,47 The junctional epithelium becomes densely infil-
trated with neutrophils, as does the gingival sulcus, and the junc-
PMN tional epithelium may begin to show the development of rete pegs
or ridges.

The amount of collagen destruction also increases12,28,47; 70%

Figure 14-1  Human biopsy sample, experimental gingivitis. After
4 days of plaque accumulation, the blood vessels immediately
adjacent to the junctional epithelium are distended and contain
polymorphonuclear leukocytes (neutrophils) (PMNs). Neutrophils
have also migrated between the cells of the junctional epithelium
(JE). OSE, Oral sulcular epithelium. (×500.) (From Payne WA, Page
RC, Ogilvie AL, et al: J Periodontal Res 10:51, 1975.)
The character and intensity of the host response determine
whether this initial lesion resolves rapidly, with the restoration of
the tissue to a normal state; alternatively, it may evolve into a
chronic inflammatory lesion. If the latter occurs, an infiltrate of
macrophages and lymphoid cells appears within a few days.
Stage II Gingival Inflammation:
The Early Lesion
The early lesion evolves from the initial lesion within about 1 week
after the beginning of plaque accumulation.35,41 Clinically, the early
lesion may appear as early gingivitis, and it overlaps with and
evolves from the initial lesion with no clear-cut dividing line. As
time goes on, clinical signs of erythema may appear, mainly
because of the proliferation of capillaries and the increased forma-
tion of capillary loops between rete pegs or ridges (Figure 14-5).
Bleeding on probing may also be evident.1 Gingival fluid flow and
the numbers of transmigrating leukocytes reach their maximum
between 6 and 12 days after the onset of clinical gingivitis.26
of the collagen is destroyed around the cellular infiltrate. The main
fiber groups that are affected appear to be the circular and dento-
gingival fiber assemblies. Alterations in blood vessel morphologic
features and vascular bed patterns have also been described.18,19
PMNs that have left the blood vessels in response to chemotac-
tic stimuli from plaque components travel to the epithelium and
cross the basement lamina; they are found in the epithelium,
emerging in the pocket area (see Figure 14-3). PMNs are attracted
to bacteria and engulf them during the process of phagocytosis
(Figure 14-6). PMNs release their lysosomes in association with
the ingestion of bacteria.23 Fibroblasts show cytotoxic alterations,40
with a decreased capacity for collagen.
Meanwhile, on the opposite side of molecular events, collagen
degradation is related to matrix metalloproteinases (MMPs). Dif-
ferent MMPs are responsible for extracellular matrix remodeling
within 7 days of inflammation, which is directly related to MMP-2
and MMP-9 production and activation.54
Stage III Gingival Inflammation:
The Established Lesion
Over time, the established lesion evolves. It is characterized by a
predominance of plasma cells and B lymphocytes, and it is prob-
ably in conjunction with the creation of a small gingival pocket
lined with a pocket epithelium.46 The B cells that are found in the
established lesion are predominantly of the immunoglobulin G1
and G3 subclasses.36
With chronic gingivitis, which occurs 2 to 3 weeks after the
beginning of plaque accumulation, the blood vessels become
engorged and congested, venous return is impaired, and the blood
flow becomes sluggish (Figure 14-7). The result is localized gin-
gival anoxemia, which superimposes a somewhat bluish hue on the
reddened gingiva.17 The extravasation of erythrocytes into the con-
nective tissue and the breakdown of hemoglobin into its component

Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
 CHAPTER 14  Gingival Inflammation 221

JE

Figure 14-2  Human biopsy, experimental gingivitis. V

A, Control biopsy specimen from a patient with good
oral hygiene and no detectable plaque accumulation.
The junctional epithelium is on the left. The connec-
CT
tive tissue (CT) shows few cells other than fibroblasts,
blood vessels, and a dense background of collagen
fibers. (×500.) B, Biopsy specimen taken after 8 days
of plaque accumulation. The connective tissue is infil-
trated with inflammatory cells, which displace the col-
lagen fibers. A distended blood vessel (V) is seen in
the center. (×500.) C, After 8 days of plaque accumu-
lation, the connective tissue next to the junctional epi- A B
thelium at the base of the sulcus shows a mononuclear
cell infiltrate and evidence of collagen degeneration JE
(i.e., clear spaces around the cellular infiltrate). (×500.)
D, The inflammatory cell infiltrate at higher magnifi-
cation (×1250). After 8 days of plaque accumulation,
numerous small (SL) and medium-sized (ML) lympho- SL
cytes are seen within the connective tissue. Most of
the collagen fibers around these cells have disap-
peared, presumably as a result of enzymatic digestion.
(From Payne WA, Page RC, Ogilvie AL, et al: J Periodontal
Res 10:51, 1975.) ML

C D

pigments can also deepen the color of the chronically inflamed

gingiva. The established lesion can be described as moderately to
severely inflamed gingiva.
In histologic sections, an intense and chronic inflammatory reaction
is observed. Several detailed cytologic studies have been performed
on chronically inflamed gingiva.13-15,40,46,49,53 A key feature that dif-
ferentiates the established lesion is the increased number of plasma
cells, which become the preponderant inflammatory cell type.
Plasma cells invade the connective tissue not only immediately
below the junctional epithelium but also deep into the connective
tissue, around the blood vessels, and between the bundles of col-
lagen fibers.6 The junctional epithelium reveals widened intercel-
lular spaces that are filled with granular cellular debris, including
lysosomes derived from disrupted neutrophils, lymphocytes, and
monocytes (Figure 14-8). The lysosomes contain acid hydrolases that
can destroy tissue components. The junctional epithelium develops
rete pegs or ridges that protrude into the connective tissue, and the
basal lamina is destroyed in some areas. In the connective tissue,
collagen fibers are destroyed around the infiltrate of intact and
disrupted plasma cells, neutrophils, lymphocytes, monocytes, and
mast cells (Figure 14-9).
The predominance of plasma cells is thought to be a primary
characteristic of the established lesion. However, several studies of
human experimental gingivitis have failed to demonstrate plasma
cell predominance in the affected connective tissues,7,8,49 including
one study of 6 months’ duration.1 Increases in the proportions of
plasma cells were evident with longstanding gingivitis, but the time
for the development of the classic “established lesion” may exceed
6 months.
An inverse relationship appears to exist between the number of
intact collagen bundles and the number of inflammatory cells.51

Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
222 PART 1  Biologic Basis of Periodontology

EC L

EC

Figure 14-6  Scanning electron micrograph of a leukocyte emerg-

Figure 14-3  Scanning electron micrograph showing a leukocyte
traversing the vessel wall to enter into the gingival connective ing to the pocket wall and covered with bacteria and extracellular
tissue. lysosomes. B, Bacteria; EC, epithelial cells; L, lysosomes.

Figure 14-7  Marginal supragingival plaque and gingivitis.

Figure 14-4  Early human gingivitis lesion. There is an area of

lamina propria subjacent to the crevicular epithelium that shows a
capillary with several extravascular lymphocytes and one lympho-
cyte within the lumen. The specimen also exhibits a considerable
loss of perivascular collagen density. (×2500.) (Courtesy Dr. Charles
Cobb, Kansas City, MO.)

Figure 14-8  Established gingivitis in a human subject. An area of

crevicular epithelium exhibits enlarged intercellular spaces with
numerous microvilli and desmosomal junctions. Several lympho-
cytes, both small and large, are seen migrating through the epithe-
Figure 14-5  Marginal gingivitis and irregular gingival contour. lial layer. (×3000.)

Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.

Figure 14-9  Advanced gingivitis in a human subject. This speci-
men from the lamina propria exhibits plasma cell degeneration,
with abundant cellular debris visible. (×3000.) (Courtesy Dr. Charles
Cobb, Kansas City, MO.)
Collagenolytic activity is increased in inflamed gingival tissue16 by
the enzyme collagenase. Collagenase is normally present in gingi-
val tissues5; it is produced by some oral bacteria and by PMNs.
Enzyme histochemistry studies have shown that chronically
inflamed gingivae have elevated levels of acid and alkaline
phosphatase,55 β-glucuronidase, β-glucosidase, β-galactosidase,
esterases,29 aminopeptidase,33,42 and cytochrome oxidase.9 Neutral
mucopolysaccharide levels are decreased,53 presumably as a result
of degradation of the ground substance.
Established lesions of two types appear to exist; some remain
stable and do not progress for months or years,32,33,52 and others
seem to become more active and to convert to progressively
destructive lesions. In addition, the established lesions appear to
be reversible in that the sequence of events that occurs in the tissues
as a result of successful periodontal therapy seems to be essentially
the reverse of the sequence of events observed as gingivitis devel-
ops. As the flora reverts from that characteristically associated with
destructive lesions to that associated with periodontal health, the
percentage of plasma cells decreases greatly, and the lymphocyte
population increases proportionately.27,31
Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
CHAPTER 14  Gingival Inflammation 223
Stage IV Gingival Inflammation:
The Advanced Lesion
The extension of the lesion into alveolar bone characterizes the
fourth stage, which is known as the advanced lesion40 or phase of
periodontal breakdown.26 This is described in detail in Chapters
21 and 23.
Microscopically, fibrosis of the gingiva is present, and there are
widespread manifestations of inflammatory and immunopathologic
tissue damage.36 At the advanced stage, the presence of plasma
cells dominates the connective tissue, and neutrophils continue
dominating the junctional epithelium.
Patients with experimental gingivitis had significantly more
plaque accumulation, higher interleukin-1β levels, and lower
interleukin-8 concentrations at 28 days.11
Gingivitis will progress to periodontitis only in individuals who
are susceptible. Patients who had sites with consistent bleeding
(gingival index = 2) had 70% more attachment loss as compared
with sites that were not inflamed consistently (gingival index = 0).
Teeth with noninflamed sites consistently had a 50-year survival
rate of 99.5%, whereas teeth with consistently inflamed gingiva
had a 63.4% survival rate over 50 years. On the basis of this lon-
gitudinal study of the natural history of periodontitis in a well-
maintained male population, persistent gingivitis represents a risk
factor for periodontal attachment loss and for tooth loss.22 However,
whether periodontitis can occur without a precursor of gingivitis is
not known at this time.
Suggested Readings
Deinzer R, Weik U, Kolb-Bachofen V, et al: Comparison of experimental
gingivitis with persistent gingivitis: differences in clinical parameters
and cytokine concentrations. J Periodontal Res 2(4):318–324, 2007.
Lang NP, Schätzle MA, Löe H: Gingivitis as a risk factor in periodontal
disease. J Clin Periodontol 36(Suppl 10):3–8, 2009.
Listgarten MA, Hellden L: Relative distribution of bacteria at clinically
healthy and periodontal diseased sites in humans. J Clin Periodontol
5:115, 1978.
Lorencini M, Silva JA, de la Hoz CL, et al: Changes in MMPs and inflam-
matory cells in experimental gingivitis. Histol Histopathol 24(2):157–
166, 2009.
Page RC, Schroeder HE: Pathogenesis of inflammatory periodontal disease:
a summary of current work. Lab Invest 34:235, 1976.
References
  References for this chapter are found on the companion
website www.expertconsult.com.

References
1. Amato R, Caton J, Polson A, et al: Interproximal gingival inflamma-
tion related to the conversion of a bleeding to a nonbleeding state.
J Periodontol 57:63, 1986.
2. Attström R: Studies on neutrophil polymorphonuclear leukocytes at the
dento-gingival junction in gingival health and disease. J Periodontal
Res 8(Suppl):1, 1971.
3. Attström R: The roles of gingival epithelium and phagocytosing
leukocytes in gingival defense. J Clin Periodontol 2:25, 1975.
4. Attström R, Egelberg J: Emigration of blood neutrophils and mono-
cytes into the gingival crevices. J Periodontal Res 5:48, 1970.
5. Beutner EH, Triftshauser C, Hazen SP: Collagenase activity of gingival
tissue from patients with periodontal disease. Proc Soc Exp Biol Med
121:1082, 1966.
6. Brecx MC: Histophysiology and histopathology of the gingiva. J West
Soc Periodontol 39:33, 1991.
7. Brecx MC, Frohlicher I, Gehr P, et al: Stereological observations on
long-term experimental gingivitis in man. J Clin Periodontol 15:621,
1988.
8. Brecx MC, Lehmann B, Siegwart CM, et al: Observations on the initial
stages of healing following human experimental gingivitis: a clinical
and morphometric study. J Clin Periodontol 15:123, 1988.
9. Burstone MS: Histochemical study of cytochrome oxidase in normal
and inflamed gingiva. Oral Surg Oral Med Oral Pathol 13:1501, 1960.
10. Caffesse RG, Nasjleti CE: Enzymatic penetration through intact sulcu-
lar epithelium. J Periodontol 47:391, 1976.
11. Deinzer R, Weik U, Kolb-Bachofen V, et al: Comparison of experimen-
tal gingivitis with persistent gingivitis: differences in clinical param-
eters and cytokine concentrations. J Periodontal Res 2(4):318–324,
2007.
12. Flieder DE, Sun CN, Schneider BC: Chemistry of normal and inflamed
human gingival tissues. Periodontics 4:302, 1966.
13. Freedman HL, Listgarten MA, Taichman NS: Electron microscopic
features of chronically inflamed human gingiva. J Periodontal Res
3:313, 1968.
14. Garant PR, Mulvihill JE: The fine structure of gingivitis in the beagle.
III. Plasma cell infiltration of the subepithelial connective tissue.
J Periodontal Res 7:161, 1971.
15. Gavin JB: Ultrastructural features of chronic marginal gingivitis.
J Periodontal Res 5:19, 1970.
16. Hancock EB, Cray RJ, O’Leary TJ: The relationship between gingival
crevicular fluid and gingival inflammation: a clinical and histologic
study. J Periodontol 50:13, 1979.
17. Hanioka T, Shizukuishi S, Tsunemitsu A: Changes in hemoglobin con-
centration and oxygen saturation in human gingiva with decreasing
inflammation. J Periodontol 62:366, 1991.
18. Hock J, Nuki K: A vital microscopy study of the morphology of normal
and inflamed gingiva. J Periodontal Res 6:81, 1971.
19. Kindlova M: Changes in the vascular bed of the marginal periodontium
in periodontitis. J Dent Res 44:456, 1965.
20. Lamster IB, Hartley LJ, Vogel RI: Development of a biochemical
profile for gingival crevicular fluid: methodological considerations and
evaluation of collagen-degrading and ground substance-degrading
enzyme activity during experimental gingivitis. J Periodontol 56:13,
1985.
21. Lamster IB, Vogel RI, Hartley LJ, et al: Lactate dehydrogenase, beta-
glucuronidase and arylsulfatase activity in gingival crevicular fluid
associated with experimental gingivitis in man. J Periodontol 56:139,
1985.
22. Lang NP, Schätzle MA, Löe H: Gingivitis as a risk factor in periodontal
disease. J Clin Periodontol 36(Suppl 10):3–8, 2009.
23. Lange D, Schroeder HE: Cytochemistry and ultrastructure of gingival
sulcus cells. Helv Odontol Acta 15:65, 1971.
24. Levy BM, Taylor AC, Bernick S: Relationship between epithelium and
connective tissue in gingival inflammation. J Dent Res 48:625, 1969.
25. Lindhe J, Socransky SS: Chemotaxis and vascular permeability pro-
duced by human periodontopathic bacteria. J Periodontal Res 14:138,
1979.
Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
CHAPTER 14  Gingival Inflammation 223.e1
26. Lindhe J, Hamp SE, Löe H: Experimental periodontitis in the beagle
dog. Int Dent J 23:432, 1973.
27. Lindhe J, Parodi R, Liljenberg B, et al: Clinical and structural
alterations characterizing healing gingiva. J Periodontal Res 13:410,
1978.
28. Lindhe J, Schroeder HE, Page RC, et al: Clinical and stereologic analy-
sis of the course of early gingivitis in dogs. J Periodontal Res 9:314,
1974.
29. Lisanti VF: Hydrolytic enzymes in periodontal tissues. Ann N Y Acad
Sci 85:461, 1960.
30. Listgarten MA, Ellegaard B: Experimental gingivitis in the monkeys:
relationship of leukocyte counts in junctional epithelium, sulcus depth,
and connective tissue inflammation scores. J Periodontal Res 8:199,
1973.
31. Listgarten MA, Hellden L: Relative distribution of bacteria at clinically
healthy and periodontal diseased sites in humans. J Clin Periodontol
5:115, 1978.
32. Lovdal A, Arno A, Waerhaug J: Incidence of clinical manifestations
of periodontal disease in light of oral hygiene and calculus formation.
J Am Dent Assoc 56:21, 1958.
33. Mori M, Kishiro A: Histochemical observation of aminopeptidase
activity in the normal and inflamed oral epithelium. J Osaka Univ Dent
School 1:39, 1961.
34. Oliver RC, Holm-Pederen P, Löe H: The correlation between clinical
scoring, exudate measurements and microscopic evaluation of inflam-
mation in the gingiva. J Periodontol 40:201, 1969.
35. Page RC: The role of inflammatory mediators in the pathogenesis of
periodontal disease. J Periodontal Res 26:230, 1991.
36. Page RC: Gingivitis. J Clin Periodontol 13:345, 1986.
37. Page RC, Schroeder HE: Pathogenesis of inflammatory periodontal
disease: a summary of current work. Lab Invest 34:235, 1976.
38. Page RC, Schroeder HE: Pathogenic mechanisms. In Schluger S,
Youdelis R, Page RC, editors: Periodontal disease: basic phenomena,
clinical management and restorative interrelationships, Philadelphia,
1977, Lea & Febiger.
39. Page RC, Schroeder HE: Periodontitis in man and other animals: a
comparative review, Basel, 1982, S Karger.
40. Page RC, Simpson DM, Ammons WF: Host tissue response in chronic
inflammatory periodontal disease. IV. The periodontal and dental status
of a group of aged great apes. J Periodontol 46:144, 1975.
41. Payne WA, Page RC, Ogilvie AL, et al: Histopathologic features of the
initial and early stages of experimental gingivitis in man. J Periodontal
Res 10:51, 1975.
42. Quintarelli G: Histochemistry of the gingiva. III. The distribution of
amino-peptidase in normal and inflammatory conditions. Arch Oral
Biol 2:271, 1960.
43. Ryder MI: Histological ultrastructural characteristics of the periodontal
syndrome in the rice rat. I. General light microscopic observations and
ultrastructural observations of initial inflammatory changes. J Peri-
odontal Res 15:502, 1980.
44. Saglie R, Newman MG, Carranza FA, Jr, et al: Bacterial invasion of
gingiva in advanced periodontitis in humans. J Periodontol 53:217,
1982.
45. Schroeder HE: Transmigration and infiltration of leucocytes in human
junctional epithelium. Helv Odontol Acta 17:6, 1973.
46. Schroeder HE, Graf-de Beer M, Attström R: Initial gingivitis in dogs.
J Periodontal Res 10:128, 1975.
47. Schroeder HE, Munzel-Pedrazzoli S, Page RC: Correlated morphomet-
ric and biochemical analysis of gingival tissue in early chronic gingi-
vitis in man. Arch Oral Biol 18:899, 1973.
48. Schwartz J, Stinson FL, Parker RB: The passage of tritiated bacterial
endotoxin across intact gingival crevicular epithelium. J Periodontol
43:270, 1972.
49. Seymour GJ, Powell RN, Aitken JF: Experimental gingivitis in
humans: a clinical and histological investigation. J Periodontol 54:522,
1983.
50. Seymour GJ, Powell RN, Cole KL, et al: Experimental gingivitis in
humans: a histochemical and immunological characterization of the
lymphoid cell subpopulations. J Periodontal Res 18:375, 1983.
223.e2 PART 1  Biologic Basis of Periodontology

51. Simpson DM, Avery BE: Histopathologic and ultrastructural features
of inflamed gingiva in the baboon. J Periodontol 45:500, 1974.
52. Suomi JD, Smith LW, McClendon BJ: Marginal gingivitis during a
sixteen-week period. J Periodontol 42:268, 1971.
53. Thilander H: Epithelial changes in gingivitis: an electron microscopic
study. J Periodontal Res 3:303, 1968.
54. Vardar-Sengul S, Arora S, Baylas H, et al: Expression profile of human
gingival fibroblasts induced by interleukin-1beta reveals central role of
nuclear factor-kappa B in stabilizing human gingival fibroblasts during
inflammation. J Periodontol 80(5):833–849, 2009.
55. Winer RA, O’Donnell LJ, Chauncey HH, et al: Enzyme activity in
periodontal disease. J Periodontol 41:449, 1970.

Downloaded for Chaerita Maulani (chaerita.maulani71@gmail.ui.ac.id) at Universitas Indonesia from ClinicalKey.com by Elsevier on April 03, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.