Scandinavian Journal of Urology and Nephrology, 2008; 42: 63
65

ORIGINAL ARTICLE

Local defense systems in the prepuce

AYŞE BALAT1, METİN KARAKÖK2, ELİF GÜLER1, NEVZAT UÇANER3 &

YASEMİN KİBAR2

Departments of 1Pediatric Nephrology, 2Pathology, Medical Faculty, Gaziantep University and 3Pediatric Surgery, Gaziantep
Children’s Hospital, Gaziantep, Turkey

Abstract
Objective. Urinary tract infection (UTI) is a common bacterial infection in children. Circumcision reduces the incidence of
UTI, and prevents preputial colonization with uropathic bacteria in childhood. However, there is insufficient information
about the reason(s) why such colonization tends to occur in prepucium skin. Material and methods. We evaluated some of the
humoral and cellular defense systems in the prepucium skins of 30 boys (age range 6 months to 5 years). We measured the
expressions of Langerhans cells, mast cells, T lymphocytes, IgA, IgG and IgM in the prepuce and compared them with those
in normal skin. Tissues obtained during circumcision were divided into two groups. In the first group, sections were stained
with hematoxylin
eosin and toluidine blue. Immunohistochemical reactions were performed on paraffin-embedded tissue
by means of the avidin
biotin
peroxidase complex method. The antibodies used were S-100 for Langerhans cells and
CD8 and CD4 for T lymphocytes. In the second group, frozen sections were stained for IgA, IgG and IgM using an
immunofluorescence method. Results. The distribution of mast cells and IgG positivity was similar to that of normal skin.
Langerhans cells were increased in prepucium skin (pB0.05), whilst only a few CD4 T lymphocytes were observed around
the perivascular area and no expression of CD8 was observed in the prepucium and normal skin. Conclusions. The increase
in Langerhans cells in prepucium skin may be the result of continuous stimulation of bacteria found in the periurethral area,
and the absence of CD8 may help the colonization of uropathic bacteria.

Key Words: Circumcision, immunity, urinary tract infection, children

Introduction Material and methods

Urinary tract infection (UTI) is a common bacterial
infection in children. Circumcision reduces the
incidence of UTI, and prevents preputial coloniza-
tion with uropathic bacteria in childhood [1].
Neonatal circumcision also facilitates the mainte-
nance of genital hygiene and may prevent local
infections such as balanoposthitis [2]. In addition,
it has been claimed that, in circumcised men and
their female sexual partners, carcinoma of the penis
and uterine cervix are less prevalent [2,3]. However,
there is insufficient information about the reason(s)
why the prepucium skin tends to be colonized with
uropathic bacteria. In this study, we firstly evaluated
some of the humoral and cellular defense systems in
prepucium skin, and compared them with those in
normal skin.
Prepucium skins of 30 boys (mean age 3.9992.30
years; age range 6 months to 5 years) were evaluated.
Informed consent was obtained from the parents of
all the subjects.
In all the subjects, skin cultures from under the
foreskin were obtained before circumcision and
urine cultures were obtained after the routine
sterilization procedure.
Tissues taken during circumcision were divided
into two groups. In the first group, tissues were
fixed in 10% neutral buffered formalin prior
to routine processing and embedded blocking. Sec-
tions were cut at a thickness of 4 mm and stained
using hematoxylin
eosin or toulidine blue (for mast
cells). Immunohistochemical reactions were per-
formed on paraffin-embedded tissue using the

Correspondence: Ayşe Balat, MD, Department of Pediatric Nephrology, Medical Faculty, Gaziantep University, PK:34, 27310 Gaziantep, Turkey. Tel: 90
342 360 60 60, ext. 76421. Fax: 90 342 335 73 74. E-mail: abalat@gantep.edu.tr

(Received 6 December 2006; accepted 16 May 2007)

ISSN 0036-5599 print/ISSN 1651-2065 online # 2008 Taylor & Francis
DOI: 10.1080/00365590701472663
64 A. Balat et al.
avidin
biotin
peroxidase complex method. Postmor-
tem skin tissue specimens obtained from 11 children
(four with multiple congenital abnormalities, three
with dilated cardiomyopathy, two with encephalitis
and two with central nervous system malignancies)
served as normal controls. Skin biopsy was per-
formed within 30 min after death. Before the skin
biopsy, we also obtained skin cultures by rubb-
ing. We measured the expressions of Langerhans
cells in epidermis, mast cells in dermis and T lym-
phocytes in both. We also determined IgA, IgG and
IgM positivity in the epidermis. The antibodies used
were S-100 for Langerhans cells and CD4 and CD8
for T lymphocytes. Langerhans cells, mast cells and
T lymphocytes were counted per square millimeter.
In the second group, frozen sections were stained
for IgA, IgG, and IgM using an immunofluorescence
method. Positivity in the tissue was recorded as
either weak, moderate or severe.
Statistical methods
Results are presented as mean9SD. Differences
between groups were compared by means of the
Mann
Whitney U-test. pB0.05 was considered
statistically significant. Statistical analysis was per-
formed using SPSS software (version 10.0; SPSS
Inc., Chicago, IL).
Results
Urine cultures were negative in all children. The
main microorganisms obtained from under the fore-
skin were Escherichia coli (36.4%), Proteus spp.
(30.3%), Enterobacter spp. (12.1%), Staphylococ-
cus aureus (12.1%), and Klebsiella spp. (9.1%).
Staphylococcus epidermidis and Streptococcus spp.
were obtained similarly in both normal skin cultures
and postmortem skin culture specimens.
The distributions of mast cells and IgG positivity
were similar to those in normal skin. IgA and IgM
were negative in all specimens. However, Langer-
hans cells were increased in prepucium skin (189.79
139.8 vs 144.59102.4 cells/mm2; pB0.05). Only a
few CD4 T lymphocytes were observed around the
perivascular area, while no expression of CD8 was
observed in the prepucium and normal skin. The
distribution of mast cells was 26.70910.79 cells/
mm2 in prepucium skin, and 21.299.7 cells/mm2 in
normal skin (p0.05).
Discussion
The skin is a highly differentiated organ; its principal
function is to act as a barrier protecting the body
against harmful exogenous pathogens [4]. Although
it is known that circumcision prevents preputial
colonization with uropathic bacteria in infancy and
childhood, there is no enough information about the
reason(s) why such colonization tends to occur
in prepucium skin. Pyelonephritogenic fimbriated
E. coli bind avidly to the inner lining of the prepuce
within the first few days of life [5
7]. Other bacteria
that attach preferentially to the mucosal surface of
the foreskin include fimbriated strains of Proteus
mirabilis and non-fimbriated Pseudomonas, Kleb-
siella and Serratia spp. [5,7,8]. Langerhans cells
(LCs) are present in the epidermis at a concentration
of 460
1000 cells/mm2. They play an important role
in the skin’s immune system [9]. Recently it has been
shown [10] that dermal LCs are in close contact with
CD4/CD45RO lymphocytes. Although the sig-
nificance of dermal LCs in inflammatory lesions
remains obscure, they are paradigmatic dendritic
cells present in the skin and in oral and bronchial
mucosa [11]. Precursor LCs migrate to the epider-
mis via the hematogenous route. After antigen
capture, LCs migrate to the regional lymph nodes
and convert into mature dendritic cells capable of
priming naive T cells [11]. In the present study, we
suggest that the increased number of LCs in the
prepuce may be the result of chronic stimulation
of colonized Gram-positive and -negative bacteria in
this area.
Normal skin contains small numbers of perivascu-
lar T cells, with the helper subtype predominat-
ing as part of the skin immune system [9]. The
T lymphocyte is the effector cell for cellular immu-
nity, while the B lymphocyte mediates humoral
immunity [9]. Interestingly, we observed that, despite
colonization by Gram-positive and -negative bacteria
under the foreskin, the expressions of CD4 and CD8
in the prepuce were similar to those in normal skin.
Conclusions
An increased level of LCs in the prepuce may be the
result of continuous stimulation of bacteria found in
the periurethral area. However, despite colonization
by different bacteria, the similar expressions of CD4
and CD8 in the prepuce and normal skin may help
the colonization of uropathic bacteria under the
foreskin.
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