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WELLNESS AND ENVIRONMENT
CHAPTER IV
1
Department of Haematology and Internal Diseases
Dr Jan Biziel University Hospital No. 2 in Bydgoszcz
2
Department of Pathophysilogy Nicolaus Copernicus University in Toruń,
L. Rydygier Collegium Medicum in Bydgoszcz
3
Clinical Ward of Vascular Diseases and Internal Medicine,
Dr Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
4
Department of Endocrinology and Diabetology, Nicolaus Copernicus
University in Toruń, Collegium Medicum in Bydgoszcz, Poland
GRAŻYNA GADOMSKA1, KATARZYNA STANKOWSKA2,
JOANNA BOINSKA2, ANITA KOWALEWSKA2,
BARBARA GÓRALCZYK2, RADOSŁAW WIECZÓR3,
DANUTA SZADZIEWSKA-KOWALSKA1, ZOFIA RUPRECHT4,
BARBARA RUSZKOWSKA-CIASTEK2, DANUTA ROŚĆ2
UPAR, u-PA and PAI-2 in blood and in lymphocytes
of patients with B-cell chronic lymphocytic leukemia
UPAR, u-PA i PAI-2 we krwi i w limfocytach chorych
na przewlekłą białaczkę limfatyczną typu 2
INTRODUCTION
Haemostasis is a set of processes responsible for stopping the bleeding after
damage to endothelial integrity (it is responsible for blood clotting), as well as for
the maintenance of vascular patency and blood fluidity for which the fibrinolytic
system is responsible [11]. Under physiological conditions processes of coagulation
and fibrinolysis remain in a state of dynamic equilibrium, which could be disrupted
in many pathological conditions, including cancer [11, 12].
Clinical observation made in recent years concerning the course of cancer have
provided much information about the pathogenic relation of haemostatic system and
cancer [7, 13, 23]. Influence of tumor cells on host organism can manifest by a presence of blood hypercoagulability, changes in the form of bleeding disorders, as well
as disorders of the fibrinolytic system [23].
HEALTH AND WELLNESS 2/2013
Wellness and environment
The essence of fibrinolysis process is the activation of plasminogen and transformation of it into an enzymatically active plasmin responsible mainly for removal
of fibrin deposits by converting it to fibrin degradation products (FDPs). This process is catalyzed by two activators: tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) [19]. It is believed that process of converting
plasminogen into plasmin which is catalyzed by t-PA is associated primarily with
dissolution of fibrin in the vascular injury site, thus maintaining the fluidity of circulating blood. On the other hand, merging of u-PA and its specific uPA receptor
(uPAR) on the cell membrane determines an increased activity of plasminogen on
the cell surface and initiates the cascade reaction of proteolysis, near the cells. This
process results in the breakdown of bonds between the extracellular matrix proteins
and in creation of a favorable environment for cell migration [4, 23]. Involvment of
urokinase plasminogen activator in the process of formation of new blood vessels in
cancer was also proven. Release of proangiogenic factors such as vascular endothelial growth factor (VEGF) induce the transformation of inactive prourokinase into
urokinase plasminogen activator on endothelial cell surface. This leads to activation
of plasminogen and plasmin production, which causes lysis of fibrin deposits in
endothelial cell migration site (EC). Degradation products of fibrinogen and fibrin
are mitogenic factors for EC and through an increase of availability of tissue factor
(TF) they lead to further activation of coagulation [16, 25].
Activity of the fibrinolytic system in physiological conditions is strictly controlled by inhibitors, mainly PAI-1 (plasminogen activator inhibitor type 1) and PAI2 (plasminogen activator inhibitor type 2). Both inhibitors are glycoproteins belonging to the family of serine protease inhibitors - the serpins. Primary function of PAI1 and PAI-2 is the inhibition of plasminogen activators. It is believed that PAI-1 is
the main inhibitor of t-PA, and PAI-2 is primarily responsible for inhibiting the
urokinase plasminogen activator (u-PA) [14, 30].
PAI-2 protein with molecular weight of 60 kD, is constituted by polypeptide
chain which takes the form of intracellular nonglycosyl, as well as secretory glycosyl. Presence of plasminogen activator inhibitor type 2 was detected firstly in the
placenta and pregnant women's plasma, and then in monocytes and macrophages.
PAI-2 concentration in plasma of healthy persons is at the limit of detection [1, 17,
31].
Many articles on the subject of fibrinolytic system abnormalities in cancer point
to an existence of correlation between high levels of PAI-1 and high degree of tumor
malignancy and poor prognosis. It was confirmed that the plasminogen activator
inhibitor type 1 is an important prognostic factor especially in breast cancer, cervical
cancer, stomach cancer and lungs cancer. Much is known about role of PAI-1 in
cancer but the importance of the second main inhibitor of fibrinolysis – PAI-2 - is
still poorly understood [20, 26].
In patients with hematological proliferative disorders there was a confirmed
presence of disturbances of coagulation and fibrinolytic systems. Cause of this may
be a protein enzyme especially fibrinolytic system elements present in white blood
60
Grażyna Gadomska, Katarzyna Stankowska, Joanna Boinska, Anita Kowalewska,
Barbara Góralczyk, Radosław Wieczór, Danuta Szadziewska-Kowalska,
Zofia Ruprecht, Barbara Ruszkowska-Ciastek, Danuta Rość
UPAR, u-PA and PAI-2 in blood and in lymphocytes
of patients with B-cell chronic lymphocytic leukemia
cells. It has been shown that cancer cells have more fibrinolytic potential than normal cells in physiological conditions [6].
A review of literature shows that most publications focus on the role of fibrinolytic system in patients with solid tumors but studies of cancer cells in leukemia including chronic lymphocytic leukemia – are rare.
The aim of this study was to assess urokinase plasminogen activator (u-PA),
uPAR and plasminogen activator inhibitor type 2 (PAI-2) in the blood and in homogenates of lymphocytes isolated from patients with chronic lymphocytic leukemia.
MATERIAL AND METHODS
The study group consisted of 45 patients with chronic lymphocytic leukemia
(M/F:29/16), treated at the Department of Hematology, University Hospital No. 2. J.
Biziel in Bydgoszcz. They were aged from 36 to 80 years (average 63,2).
Based on history, physical examination and additional tests (complete blood
count with peripheral blood smear and concentration of lactate dehydrogenase
(LDH)) the diagnosis of CLL was made. In some cases histological examination of
bone marrow trephine biopsy and histopathological examination of lymph node was
performed. All patients had a typical immunophenotype of pan B-cell antigens:
coexpression of CD19, CD20, CD5. None of the patients had shown clinical signs
of haemorrhagic diathesis or thrombotic disease during diagnostic process. The
control group consisted of 20 healthy volunteers, age- and sex- matched.
Blood samples were taken from an anticubital vein to a plastic tube containing
3.2% sodium citrate (anticoagulant: blood - 1:9). Lymphocytes isolated from these
blood samples (using Gradisol G) were counted and then homogenized using an
ultrasonic disintegrator VC-130PB.
The following parameters were determined in the study:
- on the day of blood collection:
- activated partial thromboplastin time (aPTT),
- prothrombin time (PT),
- isolation of lymphocytes.
Fibrinolytic system was studied by measuring the following parameters (in frozen
plasma):
-
fibrinogen concentration (using colorimetric method),
D-dimer level (ELISA, Asserachrom D-Di tests),
activity of α2-antiplasmin (α2-AP) (measured with a Coag−Chrom 3003
coagulometer),
level of plasmin- α 2-antiplasmin complexes (PAP) (ELISA, Dade-Behring
tests).
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ELISA immunoassay technique was used to measure following elements of fibrinolytic system in plasma and homogenates of lymphocytes:
-
concentration of urokinase plasminogen activator antigen (u-PA:Ag),
concentration of urokinase plasminogen activator receptor antigen
(uPAR:Ag),
- concentration of plasminogen activator inhibitor type 2 antigen (PAI-2:Ag)
(American Diagnostica tests).
Analysed variables were examined statistically (using STATISTICA for Windows) on account of the compliance with the normal distribution. KolmogorovSmirnov test was used to assess the normality of the distribution. The variables show
distribution different from normal, thus the median (Me), lower quartile Q1 and
upper quartile Q3 were used for values. An exception of this is a following variable:
concentration of α 2-antiplasmin, which showed a distribution close to normal, so in
this case, the arithmetic mean (M) and standard deviation (SD) were used. Values of
p<0,05 were considered to be statistically significant.
The study obtained the approval of the local ethics committee. Each studied person was informed about the aim and nature of the study and gave written consent.
RESULTS
Analysis of the haemostatic parameters in patients with chronic lymphocytic
leukemia showed a significantly higher levels of fibrinogen, prolonged aPTT and PT
times in comparison to the controls (Table I). The same table also demonstrates that
D-dimer level and alpha2-antiplasmin activity were increased in patients with CLL
in relation to the control group, and the differences were statistically significant.
Table 1. Haemostatic parameters in patients with chronic lymphocytic
leukemia in relation to the control group
Parameters
Study group
N = 45
M/Me
Fibrinogen[g/l]
4,26
aPTT[sec]
42,40
PT[sec]
17,00
D-dimer [ug/l] 374,10
Alpha2-AP[%] 116,00
62
SD/Q1;
Q3
0,81
39,00;
46,70
15,80;
17,50
297,40;
551,90
18,75
Control group
N = 20
M/Me
3,07
39,00
16,00
265,20
96,55
SD/Q1;
Q3
0,47
33,00;
40,70
14,50;
16,40
131,90;
340,15
10,40
p
<0,0001
<0,01
<0,001
<0,001
<0,0001
Grażyna Gadomska, Katarzyna Stankowska, Joanna Boinska, Anita Kowalewska,
Barbara Góralczyk, Radosław Wieczór, Danuta Szadziewska-Kowalska,
Zofia Ruprecht, Barbara Ruszkowska-Ciastek, Danuta Rość
UPAR, u-PA and PAI-2 in blood and in lymphocytes
of patients with B-cell chronic lymphocytic leukemia
Table II contains selected parameters of the fibrinolytic system measured in the
plasma of patients and controls. The comparison indicate that u-PA:Ag level was
significantly increased in patients with CLL in relation to the controls. What's more,
the presence of the urokinase receptor (uPAR) was shown only in patients with
chronic lymphocytic leukemia. The PAI-2:Ag level was below the detection limit in
both groups.
Table II. Selected parameters of fibrinolytic system in patients with chronic
lymphocytic leukemia compared to the control group
Parameters
Study group
N = 45
M/Me
u-PA:Ag [ng/ml]
0,68
u-PAR:Ag [ng/ml] 0,14
PAI-2:Ag [ng/ml]
0,00
SD/Q1;
Q3
0,60;
0,88
0,11;
0,21
0,00;
0,00
Control group
N = 20
M/Me
0,53
0,00
0,00
p
SD/Q1;
Q3
0,46;
<0,001
0,58
0,00;
<0,0001
0,00
0,00;
0,00
0,00
Table III. The concentration of u-PA:Ag, uPAR:Ag and PAI-2:Ag per 1 lymphocytes in the study and control group
Parameters
Study group
N = 45
Control group
N = 20
p
SD/Q1;
SD/Q1;
Me
Me
Q3
Q3
117,35;
220,69;
u-PA:Ag [ag] 205,24
410,63
<0,05
369,39
424,44
95,67;
0,00;
u-PAR:Ag [ag] 135,25
0,00
<0,0001
253,85
0,00
637,29;
660,36;
PAI-2:Ag [ag] 1764,26
3951,95
0,0802
3285,15
8558,44
[ag] – mass unit, attogram, ag = 10-18 gram
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Table III indicates that u-PA:Ag concentration in lymphocytes of patients with
chronic lymphocytic leukemia was two times lower than in lymphocytes of controls.
What's interesting, the presence of the uPAR was found only in lymphocytes of
CLL patients. Slight differences in the amounts of the PAI-2:Ag in the lymphocytes
isolated from the patients and controls were statistically insignificant.
Table IV. The concentration ratio of the u-PA/1 lymphocyte : uPAR/1
lymphocyte in the study group
Study group
uPAR:ag u-PA:Ag uPAR:Ag : u-PA:Ag
[ag]/l lymphocyte 135,25 205,24
1 : 1,5
As demonstrated in table IV, in lymphocytes of CLL patients there is 1.5 times
more u-PA:Ag than uPAR. Due to the fact that in lymphocytes of healthy persons
there is only u-PA:Ag present (lack of its specific receptor – uPAR), we could not
make a similar calculation in healthy subjects.
DISCUSSION
Imbalance between the processes of coagulation and fibrinolysis is the cause of
the formation of blood clots in both micro- and macrovascular system. These
pathological conditions are shown in abnormalities of coagulation system, as well as
massive congestion that eventually may lead to the death of the patient [27].
Our study showed that in the plasma of patients with B-cell chronic lymphocytic
leukemia there is an increased level of plasma fibrinogen as well as slightly - although significantly - prolonged aPTT and PT times, elevated D-dimer level and
increased activity of a2-antiplasmin.
Fibrinogen is a plasma protein involved in platelet aggregation and influencing
blood viscosity, hence the increased concentration of this parameter in patients with
chronic lymphocytic leukemia causes a threat of blood hypercoagulability. Polterauer showed that there exists a connection between elevated fibrinogen concentration
and poor prognosis in patients with colorectal cancer, breast cancer and small-and
non-small cell lung cancer [21]. Increased level of fibrinogen was also found in
chronic myeloid leukemia, which according to Rość D. et al. may reduce the bleeding tendency in these patients [24]. Palatyńska-Ulatowska et al. emphasize that the
presence of fibrinogen and fibrin (produced by fibrinogen) affects stimulation of
tissue factor (TF; indirectly involved in angiogenesis) as well as proliferation and
migration of endothelial cells, which characterise the process of carcinogenesis [18].
In some patients with neoplasms due to the accompanying disseminated intravascular coagulation (DIC) there is secondary activation of the fibrinolytic system
[15]. Particular importance in the diagnosis of these disorders is attributed to the
determination of the concentration of D-dimers, formed in degradation of stabilized
fibrin by factor XIIIa [22]. Significantly higher concentration of this parameter was
64
Grażyna Gadomska, Katarzyna Stankowska, Joanna Boinska, Anita Kowalewska,
Barbara Góralczyk, Radosław Wieczór, Danuta Szadziewska-Kowalska,
Zofia Ruprecht, Barbara Ruszkowska-Ciastek, Danuta Rość
UPAR, u-PA and PAI-2 in blood and in lymphocytes
of patients with B-cell chronic lymphocytic leukemia
demonstrated in patients with CLL, as well as in patients with lung, breast, ovarian
and colorectal cancers [8]. An increase in the concentration of D-dimer levels in
patients diagnosed with acute leukemia was independent from the type of leukemia.
On the other hand their return to reference values or substantially reduced concentration were observed during remission of the disease [3, 5].
Elevated levels of D-dimer in plasma is a proof of the creation of fibrin and its
digestion, and in neoplasm it may indicate a disseminated intravascular coagulation.
This phenomenon also explains observed prolongated aPTT and PT times in patients with chronic lymphocytic leukemia, because degradation products of fibrinogen and fibrin (including D-dimers) inhibit coagulation [16].
A2-antiplasmin is the main physiological inhibitor of plasmin also able to inhibit
factors XIa, Xa and thrombin. Decreased activity of this inhibitor was observed in
patients with breast cancer, stomach cancer and malignant melanoma. A2-AP activity is reduced as a result of a severe process of plasmin inhibition in connection with
consumption of this inhibitor due to its insufficient synthesis in hepatocytes of patients. That was not the case in patients with chronic lymphocytic leukemia [29].
The present study showed significantly higher activity of a2-AP in the plasma of
patients with CLL than in healthy subjects. A recent study by Kanno Y. et al. points
to yet another biological role of a2-AP. It influences the synthesis of transforming
growth factor alpha (TGF-alpha). Research by Hou et al. proves that a2-AP is a
regulator of angiotensin II, which is involved in tissue remodeling. Therefore, high
activity of a2-AP in PBL may be associated with tumor angiogenesis [9, 10].
The performed study showed elevated concentration of u-PA:Ag and the presence of uPAR:Ag in plasma of patients with CLL.
Urokinase plasminogen activator plays an important role not only in physiological conditions but also pathological processes such as inflammation, tumor progression and especially in invasion and metastasis of malignant tumors. Numerous clinical studies have shown that the concentration of u-PA in different tumor samples
were significantly higher that in healthy tissue [2]. Urokinase plasminogen activator
is produced and released by tumor cells or stromal cells in proximity to the tumor as
inactive proenzyme. U-PA is activated by binding with a highly specific uPAR [6,
28]. It is believed that most of the biological properties of urokinase plasminogen
activator is a result of binding to its uPAR [6].
Numerous research have shown that increased concentration of u-PA in the
plasma of patients with esophagus, stomach, thyroid, breast and liver cancers, positively correlated with a high incidence of recurrence, poor prognosis and high mortality [2].
It has been estimated, that fibrinolysis activation in many solid tumors are of
primary fibrinolysis type whereas, in accordance to our studies high levels of u-PA,
uPAR and D-dimers in CLL patients seem rather to point to a secondary activation
of the fibrinolytic system.
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Comparing the homogenates of lymphocytes of healthy subjects and patients
showed that in lymphocytes of patients uPAR:Ag was present and the concentration
of u-PA:Ag was two times lower than in control group.
Based on the performed studies it has been estabilished that leukemic cells, as
well as better known solid tumor cells, have the ability to produce plasminogen
activators. Plasmin, as a product of a reaction catalyzed by u-PA, has a high
proteolytic activity and is responsible for converting pro-metalloproteinases to
metalloproteinases, which play a key role in the degradation of collagen. This fact
allows tumor cells to escape the primary tumor site, which facilitates the formation
of metastases [25, 28]. In the case of a metastatic tumors, this property allows tumor
cells to penetrate different tissues and organs.
Previous studies of lymphocytes in patients with CLL, conducted by Zucker S. et
al, has shown significantly reduced fibrinolytic activity of leukemic cells in 95% of
patients with CLL in comparison to normal cells. Low content of plasminogen
activators in leukemic cells was regarded at the time as pathological. Results of the
present studies are consistent with those obtained by Zucker, S. et al. However, in
our opinion, the small content of plasminogen activators in leukemic cells of
patients with CLL is a result of their release into the bloodstream [32].
It is also worth to mention that an observation made during our studies has
shown that the leukemia cells have a u-PAR receptor. Its presence is a prerequisite
for activation of uPA, which is responsible for the fibrinolysis activation allowing
degradation of the extracellular matrix and penetration of tissue by tumor leukemic
cells. It is assumed that uPA is used up in this process, which also may explain its
lower levels in leukemic cells in comparison to healthy cells.
The presence of u-PA and uPAR in lymphocytes of patients diagnosed with
chronic lymphocytic leukemia is therefore a decisive factor in regard to potential,
vast possibilities of extravascular proteolytic activation and thus the expansiveness
of leukemic cells.
Current studies indicate the involvement of fibrinolytic mechanisms in the formation of metastases in patients with chronic lymphocytic leukemia. A review of the
literature shows however that most research have so far been focused on the activity
of the fibrinolytic system components in solid tumors. Further studies are therefore
needed for better understanding of the molecular mechanisms underlying fibrinolysis in hematologic malignancies. This would allow to translate the obtained results
into the practical human diagnostic, therapeutic and prognostic tools.
CONCLUSIONS
1. Elevated plasma fibrinogen level in patients is a risk factor for thrombotic disease.
2. Elevated D-dimer and uPA levels and the presence of uPAR in blood of patients
with CLL is a proof of a secondary activation of the fibrinolytic system.
3. The presence of uPA and uPAR in lymphocytes of patients with CLL demonstrates their potential capabilities of migration to tissues and organs.
66
Grażyna Gadomska, Katarzyna Stankowska, Joanna Boinska, Anita Kowalewska,
Barbara Góralczyk, Radosław Wieczór, Danuta Szadziewska-Kowalska,
Zofia Ruprecht, Barbara Ruszkowska-Ciastek, Danuta Rość
UPAR, u-PA and PAI-2 in blood and in lymphocytes
of patients with B-cell chronic lymphocytic leukemia
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Barbara Góralczyk, Radosław Wieczór, Danuta Szadziewska-Kowalska,
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ABSTRACT
Recent years have brought an increased interest in the role of fibrinolysis system
in pathogenesis of cancer. It is believed that this is not only an accompanying
process and a cause of complications, but an integral mechanism of disease
progression and metastasis. The aim of the study was to assess urokinase plasminogen activator (u-PA), urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor type 2 (PAI-2) in homogenates of lymphocytes isolated
from patients with chronic lymphocytic leukemia (CLL). The study included 45
patients with chronic lymphocytic leukemia and 20 healthy volunteers who formed
the control group. Venous blood drawn from an anticubital vein to a plastic tube
containing 3.2% sodium citrate was used as material for study. Lymphocytes
isolated from these blood samples (using Gradisol G) were counted and then
homogenized using an ultrasonic disintegrator VC-130PB. The following
parameters were determined: activated partial thromboplastin time (aPTT),
prothrombin time (PT), fibrinogen, D-dimers, the activity of α2 - antiplasmin (α 2AP), concentration of plasmin -α2-antiplasmin complexes (PAP). ELISA immunoassay technique was used to measure following elements of fibrinolytic system in
plasma and homogenates of lymphocytes: concentration of urokinase plasminogen
activator antigen (u-PA:Ag), urokinase plasminogen activator receptor antigen
(uPAR:Ag) and plasminogen activator inhibitor type 2 antigen (PAI-2:Ag). Concentration of fibrinogen (4,26g/l) in patients was significantly higher than in control
group (3,07g/l), as was concentration of D-dimers (374,10 g/l). There was also a
notable increase in α 2-antiplasmin activity (116,60%), prolongation of aPTT
(42,40sec) and PT time (17,00sec). There was also observed a significant increase in
concentration of u-PA:Ag (0,68 ng/ml) as well as a presence of uPAR:Ag (0,14
ng/ml) in plasma of patients. Comparing the homogenates of lymphocytes of healthy
subjects and patients brought two observations: only in lymphocytes of patients
there was noted a presence of uPAR:Ag (135,25ag), but the concentration of uPA:Ag in lymphocytes of CLL patients (205,24ag) was two times lower than in
lymphocytes of controls. Increased D-dimer and uPA concentration as well as uPAR
in patients with chronic lymphocytic leukemia is a proof of secondary activation of
the fibrinolytic system and the presence of u-PA and uPAR in the lymphocytes of
CLL patients is an argument for potential migratory properties of leukemic cells.
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HEALTH AND WELLNESS 2/2013
Wellness and environment
STRESZCZENIE
Ostatnie lata przyniosły wzrost zainteresowania rolą układu fibrynolizy w
patogenezie choroby nowotworowej. Uważa się, że nie jest to tylko proces
towarzyszący i przyczyna powikłań, ale integralny mechanizm rozwoju choroby
oraz powstawania przerzutów. Celem pracy była ocena urokinazowego aktywatora
plazminogenu (u-PA), receptora uPAR oraz inhibitora typu 2 (PAI-2) w
homogenatach limfocytów izolowanych od osób chorych na przewlekłą białaczkę
limfatyczną. Badaniami objęto 45 chorych na przewlekłą białaczkę limfatyczną oraz
20 zdrowych ochotników, którzy stanowili grupę kontrolną. Materiałem
wykorzystanym do badań była krew żylna pobierana z żyły łokciowej do probówek
zawierających 3,2% cytrynian sodu. Izolowane z niej limfocyty (z zastosowaniem
Gradisolu G) były liczone, a następnie homogenizowane przy użyciu dezintegratora
ultradźwiękowego VC-130PB. Otrzymano również osocze ubogopłytkowe do oceny
układu hemostazy krwi. U osób biorących udział w badaniu wykonano następujące
oznaczenia w osoczu krwi: czas częściowej tromboplastyny po aktywacji (aPTT),
czas protrombinowy (PT), stężenie fibrynogenu, D-dimerów, aktywność 2 –
antyplazminy (2-AP), stężenie kompleksów plazmina - 2-antyplazmina (PAP). W
osoczu krwi i w homogenatach limfocytów techniką immunoenzymatyczną ELISA
oceniono: stężenie antygenu urokinazowego aktywatora plazminogenu (u-PA:Ag),
antygenu receptora urokinazowego aktywatora plazminogenu (uPAR:Ag,) oraz
antygenu inhibitora aktywatora plazminogenu typu 2 (PAI-2:Ag). Stężenie
fibrynogenu (4,26g/l) w grupie chorych było istotnie wyższe niż w grupie kontrolnej
(3,07g/l), istotnie wyższe było również stężenie D-dimerów (374,10g/l) wzmożona
aktywność 2-antyplazminy (116,60%), wydłużony czas aPTT (42,40s) i PT
(17,00s). Wykazano także istotnie wyższe stężenie u-PA:Ag (0,68ng/ml) i obecność
uPAR:Ag (0,14ng/ml) w osoczu krwi chorych. Badanie homogenatów limfocytów
od osób zdrowych oraz chorych wykazało tylko w limfocytach chorych obecność
uPAR:Ag (135,25ag), ale dwukrotnie niższe niż w grupie kontrolnej stężenie uPA:Ag (205,24ag). Podwyższone stężenie D-dimerów i uPA, a także obecność
uPAR we krwi chorych na przewlekła białaczkę limfatyczną dowodzi wtórnej
aktywacji fibrynolizy, natomiast obecność u-PA i uPAR w limfocytach pacjentów z
PBL jest argumentem przemawiającym za potencjalnymi właściwościami
migracyjnymi komórek białaczkowych.
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