The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis
The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis
Justyna Sikora 0
Agnieszka Wróblewska‑Czech 0
Marta Smycz‑Kubańska 0
Aleksandra Mielczarek‑Palacz 0
Anna Cygal 0
Andrzej Witek 0
Zdzisława KonderaA‑nasz 0
0 Department of Immunology and Serology, School of Pharmacy with the Division of Medical Analytics in Sosnowiec, Medical University of Silesia in Katowice , Jedności 8, 41-200 Sosnowiec , Poland
1 Justyna Sikora
Purpose The purpose of the work was to evaluate possible associations between the complement components C1q, mannosebinding lectin (MBL) and C1 inhibitor (C1INH) with pathogenesis of endometriosis. Methods Concentrations of C1q, MBL and C1INH were measured by ELISA in peritoneal fluid (PF) in 80 women with or without endometriosis. Results Significantly higher PF levels of C1q, MBL and C1INH in women with endometriosis compared to control group were observed (p < 0.0001). A higher concentration of the studied parameter was found in PF of women at the early stage of the disease, as compared to women with advanced endometriosis (p < 0.0001). Conclusions Our research suggests that in the peritoneal cavity in women with endometriosis there are abnormal regulations of both the classical and lectin pathways of the complement system. This can suggest impairments in purification of peritoneal cavity from ectopic endometrial cells and augmented local inflammation in endometriosis patients.
Complement components; Endometriosis; Peritoneal fluid
Introduction
Endometriosis is a common gynecological condition that
affects approximately 10–12% of female population in
reproductive age and up to 60% of infertile women [
1
]. It is
defined as the presence and growth of endometrial-like
tissues ectopically, most commonly on the pelvic peritoneum
and ovaries [
2
]. Although endometriosis was first described
more than 150 years ago, the pathogenesis of the disease
is still poorly understood. The retrograde menstruation, a
widely accepted theory, explained the possibility of
endometrial cells appearing in the peritoneal cavity, but did not
explain why cells were living there [
3
]. Recently, studies
Department of Gynecology and Obstetrics, School
of Medicine in Katowice, Medical University of Silesia
in Katowice, Medyków 14, 40-752 Katowice, Poland
have strongly suggested that local and systemic dysfunction
of the immune system and inflammation must be involved in
the survival of endometrial implants in ectopic localization
[
4
]. In a physiological condition, well-functioning immune
system mechanisms, eliminate endometrial cells from the
peritoneal cavity. However, in women with endometriosis, it
seems that the immune dysfunction and an altered peritoneal
environment are associated with the reduced clearance of
retrogradely transported endometrial fragments [
5
]. In the
peritoneal fluid (PF) a high accumulation of peritoneal
macrophages, regulatory T suppressor cells, NK cells and
cytotoxic T lymphocyte with reduced killing capacity, cytokines,
immunoglobulins (Ig) and inflammatory mediators can be
found [
6, 7
].
One of the most important immune mechanisms taking
part in the peritoneal clearance and inflammation is the
complement system. The complement, a crucial component of
the innate immune system, consists of over 30 small proteins
which act as a cascade of proteases that activate each other
in an enzymatic fashion, with effector mechanisms mediated
by several specific cell receptors [
8, 9
]. The general
function of the complement is to recognize microbial pathogens
and other target cells and let them lyse. The complement
cascade can be activated via one of three pathways: the
classical pathway, the lectin pathway and the alternative
pathway. These pathways are activated via different recognition
molecules. The alternative complement pathway is initiated
directly by the pathological organism. The classical pathway
is started by the activation of C1q, by binding to ligands
such as surface-bound IgM or IgG [10]. C1q is a plasma
glycoprotein produced mainly by a wide range of immune
cells including monocytes and macrophages, dendritic cells,
and by epithelial and endothelial cells, as well as fibroblasts
and trophoblasts [
11
]. The connection to the globular head
domain of C1q with IgG or IgM containing immune
complexes, causes an activation of C1r, which in turn activates
C1s [
8
]. The lectin pathway is like the classical pathway. The
cascade is initiated by binding of mannose-binding lectin
(MBL) to mannose contained on the surface of the target
cells. It is associated with various MBL-associated serine
proteases (MASPs), which upon activation lead to the
cleavage of C2 and C4 [
12
].
The activated C1 complex and MBL cleave the C4 and C2
components in the classical and lectin complement cascade,
resulting in the assembly of the C3 convertase (C4b2a) [
13
].
In all three pathways the sequence of reactions leads to the
generation of proteas (...truncated)