БОЛЕЗНИ ОРГАНОВ КРОВООБРАЩЕНИЯ: ФУН АМЕНТАЛЬНЫЕ

реклама
:
CIRCULATORY DISEASES: BASIC AND CLINICAL ASPECTS
616-092.18:612.017.11
–
. .
«
.
(
)
, . .
-
.
, . .
»,
,
,
(1- –
,2- –
).
, . Cd14hiCd16+ Cd14dimCd16++) 1- 7- .
. 1- Cd14hiCd16+.
3- (
Cd14hiCd16–
, Cd14hiCd16+–
, .
SofA Cd14hiCd16– Cd14hiCd16+ .
. 1- Cd14hiCd16–
.
:
,
,
.
.
-
),3- –
(Cd14hiCd16–,
(
Cd14hiCd16– )
-
Cd14hiCd16+
,
-
MONOCYTE SUBSETS IS A PREDICTOR Of SEVERE COMPLICATIONS
Of SYSTEMIC INfLAMMATORY RESPONSE AfTER CORONARY BYPASS SURGERY
V. G. MATVEEVA, A. S. GOLOVKIN, E. V. GRIGORIEV
Federal State Budgetary Institution Research Institute for Complex Issues
of Cardiovascular Diseases, Kemerovo, Russia
Purpose.thestudywasexaminingofdynamicsbloodmonocytesubsetsfrompatientswithdifferentseverityofSystemicInlammatoryResponseSyndrome(SIRS)aftercoronarybypasssurgery.
Materials and methods.Inretrospect,allofthepatientsinaccordancewithseverityoftheSIRSweredividedintothreegroups
(1–uncomplicatedSIRS,2–complicatedSIRSwithcompensatedMultipleorgandysfunctionSyndrome(ModS),3–complicatedSIRS
withdecompensatedModS).SIRSconirmedbyobjectiveclinicalandlaboratoryparameters,aswellasthepresenceofhypercytokinemia.
Eachgroupwasestimateddynamicsofmonocytesubsets(Cd14hiCd16–,Cd14hiCd16+andCd14dimCd16++)bylaserlowcytometerbefore
surgeryand1stand7thdayaftersurgery.
Results.ontheirstdayaftersurgerypatientsoftheallgroupswasdetectedtheactivationofmonocyteswiththeredistributionof
theirsubpopulationcomposition(decreaseintherelativecontentsubsetofCd14hiCd16–andincreaseinCd14hiCd16+).Atthesametime,
patientsofthethirdgroup(SIRSwithdevelopedinthefuturedecompensatedModS)subsetCd14hiCd16–waslowerandCd14hiCd16+
washigherthanintheothergroups.foundcorrelationoftheSofAestimatesandtherelativeproportionsbloodmonocytesCd14hiCd16–
andCd14hiCd16+.
Conclusion.IntheirstdaysaftercoronarybypasssurgeryrelativeproportionsubsetsCd14hiCd16+andCd14hiCd16–maybediagnosticandprognosticmarkersofthesevereSIRSanddevelopedinthefuturedecompensatedModS.
Key words: monocyte subsets, Systemic Inlammatory Response Syndrome, Multiple organ dysfunction Syndrome, prognostic
marker.
5
:
(
)
(
-
[2].
(
.
(
50 % [4].
)
,
-
)
-
)
.
(
).
-
,
(
–
–
–
38 °
20
12×10 9/
.
–
36 ° ,
90 /
;
4×109/
– -
;
10 %),
[8],
14 CD16 ,
–
[1, 2].
-
[3]
[1].
-
,
(IL-6, IL-8, TNF , IL-10)
,
,
.
-
[2].
-
CD14dimCD16++
. .
.
,
2010 .
hi
,
-
,
,
-
,
,
[16].
.
,
,
.
-
,
:
CD14hiCD16+,
[14].
CD-
,
,
[11, 13, 14].
CD14hiCD16+
,
,
,
,
dim
++
CD14 CD16
[18, 19].
CD14+CD16+,
–
,
,
(
,
,
,
,
. .) [19].
.
,
,
[2].
-
,
6
,
.
,
.
,
-
. .
, . .
, . .
(
,
)
–
(
. 1).
-
-
.
, 19
),
69
,
– 62
(55–
»
2012 . c
(
),
( ),
(
)
-
II–III
I–II
. .
45 %».
APACHEII
.
Levy.
-
,
-
,
: 1- –
).
, 2- –
, 3- –
.
.
,
:
,
.
-
,
.
,
-
POSSUM.
Bone
SOFA.
(
,
[5].
(50
«
2011 .
: «
,
...
-
[10].
.
67
3(69
,
-
(65–74), <0,05)
(1- 59 (55–65), 2- 62 (54–68).
.
-
96
– 61
(80–112,5
(53–70
–
2
.
),
).
3.
(
K3
7
,
.
-20 ° .
)
(
.
,
,
18–20
:
)
2
.
-
1
1-
SOFA,
APACHEII
POSSUM
2
–
2-
–
-
3-
–
0
1–3
4
0–5
5,
6–11
10,
12
1,2 %
4,9 %
20,
-
24,9 %
0–2
2
2–4
–
+
+++
–
+
+++
70 (68–79) %
65 (60–67) %
60 (58–67) %
7
:
4
FSC/SSC, SSC/CD45
.
eBioscience (HumanTNF- HighSensitivityELISA, HumanIL-6 PlatinumELISA, HumanIL-10
PlatinumELISA).
,
.
«
»(
).
CD14.
3
.
CD16–FITC (IQTest,
IsotypeIgG1), CD45–PC5 (IQTest, IsotypeIgG1),
CD14–APC (IQTest, IsotypeIgG2 , BeckmanCoulter, USA).
3
.
30
.
Invitrogen).
PBS.
14hiCD16–, CD14hiCD16+
– CDCD14dimCD16+ ( .).
Statistica 6.0.
-
(Wilcoxon).
–
,
.
8
(Q1–Q3)
(FS )
SSC
).
(Spearman).
( ), 25 75 %
.
-
,
(
) [2, 6, 9].
FACSCaliburBD
.
-
(U-
<0,05.
(PBSpH= 7,2 (Gibco,
CellQuestPro
.
CD16
CD14
-
(SSC)
SSC/
-
-
(
IL-6
(
20
. 2).
,
IL-6
,
CD45.
CD14
CD16
)
.
-
. .
, . .
, . .
3-
,
IL-6
2-
.
–
.
IL-10
3-
,
(
-
.
IL-10
. 2).
. 2).
(
TNF
...
.
-
2
,
(
1-
7-
I-II
I
(Q1–Q3)
II-III
II
IL-6 (
/
I-III
III
)
1 (n= 31)
1,7 (0,52–2,36)
<0,0001
38,62 (18,26–125,02)
<0,0001
3,94 (0,8–8,66)
0,0001
2 (n= 30)
1,55 (0,57–2,15)
0,0001
29,06 (18,33–63,05)
0,0002
4,75 (1,7–8,43)
0,005
3 (n= 8)
1,88 (1,58–2,35)
0,0117
78,5 (49,8–126,2)
0,0277
9 (4,3–14,32)
0,0277
##
TNF (
/
)
1
0,234 (0,210–0,287)
0,0033
0,278 (0,255–0,366)
0,0043
0,244 (0,222–0,275)
0,9063
2
0,25 (0,238–0,272)
0,0843
0,271 (0,249–0,326)
0,0995
0,252 (0,238–0,27)
0,9375
3
0,281 (0,265–0,308)
0,0679
0,315 (0,283–0,394)
0,0679
0,256 (0,255–0,303)
0,4652
1
3,17 (2,50–4,25)
<0,0001
11,20 (6,42–55,88)
<0,0001
3,60 (2,70–4,67)
0,1808
2
3,84 (2,63–5,41)
<0,0001
8,78 (5,3–30,8)
<0,0001
4,22 (3,10–4,99)
0,6272
3
4,39 (2,15–5,72)
0,0117
72,15*/** (13,93–95,61)
0,0277
4,59 (3,80–5,71)
0,051
IL-10 (
= 0,035
##
2-
2-
/
)
; * = 0,049
.
1-
; ** = 0,013
3
,
(
7-
1I
(Q1–Q3)
II
I–II
III
II–III
CD14 CD16
hi
I–III
–
1 (n= 31)
85,8 (80,1–90,5)
<0,0001
76,3 (73,3–80,8)
0,0003
85,3 (78–91,5)
0,581
2 (n= 29)
84,8 (80,1–88,8)
77,2 (69,3–85,5),
n=4
0,0169
0,0080
83,8 (81–88,3)
80,2 (76,5–83,9),
n=2
0,527
0,068
78,3 (73,5–85,9)
67,3*/** (60,7–68,7),
n=4
CD14hiCD16+
3 (n= 4)
–
–
1
4,7 (3,8–11,7)
<0,0001
18,1 (13,9–23,3)
<0,0001
5,8 (4,4–13,4)
0,052
2
6,3 (4,2–9,3)
<0,0001
18,5 (11,4–23,8)
0,0002
9,4 (5,9–11,2)
0,0214
3
9,2 (8,1–13,6)
0,0680
29 #/## (26,3–30,9)
–
11,4 (8,9–13,9)
–
2,3 (1,5–3,7)
<0,0001
3,9 (2,5–6)
0,0930
CD14dimCD16+
1
5,3 (3,6–8,1)
<0,0001
2
5,4 (4,2–10,3)
<0,0001
2,4 (2–3,6)
0,0010
4,5 (2,8–7,8)
0,0068
3
10,5 (5,5–16,7)
0,069
2,7 (2,0–7,0)
–
6,9 (4,3–9,5)
–
* = 0,007
1-
1-
; ## = 0,0177
; ** = 0,0081
2-
2-
.
; # = 0,0095
9
:
,
.
SOFA
CD14hiCD16–
CD14hiCD16–
(
-
4.
(
. 3).
1
2),
-
(+0,25
–0,25).
CD14hiCD16+,
(r)
4
SOFA
.
,
CD14hiCD16–
-
3-
,
1-
2-
.
-
(%)
SOFA (
)
CD14hiCD16–
r= –0,25 ( = 0,046)
CD14hiCD16+
r= +0,25 ( = 0,044)
CD14dimCD16+
r= +0,14 ( = 0,283)
CD14hiCD16+
(
. 3),
3-
CD14hiCD16+
,
CD14hiCD16+ (
1.
,
-
-
.
)
2-
.
-
IL-6 IL-10
-
.
CD14dimCD16+.
.
(
TNF
-
,
),
,
,
(
–
,
CD14hiCD16+
[15]
,
.
),
-
.
CD14hiCD16–.
,
.
SOFA
10
TNF
,
IL-6, TNF
IL-10
[7].
-
5–10 %
CD14hiCD16–.
,
,
,
CD14hiCD16+
-
,
,
.
,
.
CD14hiCD16–
-
. .
, . .
, . .
–
.
.
[11].
CD14hiCD16+
.
CD-
14hiCD16+
TNF , IL-1 , IL-6
[13].
-
,
»
[11].
CD14hiCD16+
CD14hiCD16–,
CD14hiCD16–
-
,
CD14hiCD16+.
,
CD14 CD16+
CD14hiCD16–
hi
-
.
-
SOFA
.
.
[7],
CD14hiCD16+
-
.
CD14hiCD16+
CD14 CD16+
68,7 %
CD14hiCD16–,
(
CD14hiCD16+,
hi
CD14hiCD16+
).
-
,
CD14hiCD16–
CD14hiCD16+,
[12, 17, 18].
CD14hiCD16+.
-
(IL-6,IL-10).
-
,
,
.
CD4 T-
,
«
...
,
-
26,3 %
.
.
1.
.
[
2. C. 9–17.
2.
.
. 9–21.
3.
. .
[
1. C. 15–23.
4.
/
123.
5.
1998.
6.
/
. 2008. . 7,
.] //
.,
. .,
//
.
. 2007. . 6,
4.
. 2008.
/
7,
.] //
. .
[
.
.]. //
.
. 2013.
2. . 119–
.
//
2. . 25–30.
. .,
.
.
.
//
. 2012. . 14, 1–2. . 9–20.
7.
. .
.
.
,
2010. 752
8. Bone R. ., Sibbald W. J., Sprung . L. The ACCP-SCCM consensus conference on sepsis and organ failure // hest.
1992. Vol. 101, 6. P. 1481–1483.
11
:
9. Evidence of systemic cytokine release in patients undergoing cardiopulmonary bypass / J. Halter [et al.] // J. Extra
Corpor. Technol. 2005. Vol. 37, 3. P. 272–277.
10. Hirai S. Systemic Inlammatory Response Syndrome
afterCardiac Surgery under Cardiopulmonary Bypass // Ann.
Thorac. Cardiovasc. Surg. 2003. Vol. 9(6). P. 365–370.
11. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors / J. Cros.
[et al.] // Immunity 2010. Vol. 33, 3. P. 375–386.
12. Immature monocytes acquire antigens from other cells
in the bone marrow and present them to T cells after maturing
in the periphery / F. Tacke [et al.] // J. ExP. Med. 2006. Vol. 203,
3. P. 583–597.
13. Monocyte heterogeneity in human cardiovascular disease / A. M. Zawada [et al.] // Immunobiology. 2012. Vol. 217,
12. P. 1273–1284.
14. Nomenclature of monocytes and dendritic cells in blood /
L. Ziegler-Heitbrock [et al.] // Blood. 2010. Vol. 116 (16).
P. 74–80.
15. Perioperative serum levels of tumour-necrosis-factor
alpha (TNF-alpha), IL-1 beta, IL-6, IL-10 and soluble IL-2
receptor in patients undergoing cardiac surgery with cardiopulmonary bypass without and with correction for haemodilution / A. Roth-Isigkeit [et al.] // Clin. Exp. Immunol. 1999.
Vol. 118, 2. P. 242–246.
16. Piccinini A. M., Midwood K. S. DAM Pening inlammation by modulating TLR signaling // Mediators of Inlammation. 2010. – pii : 672395.
17. Regulation of Toll-like receptor (TLR)2 and TLR4 on
CD14dimCD16+ monocytes in response to sepsis-related antigens / N. A. Skinner [et al.] // Clin. Exp. Immunol. 2005.
Vol. 141(2). P. 270–278.
18. Senescent CD14+ CD16+ Monocytes Exhibit Proinlammatory and Proatherosclerotic Activity / A Merino [et al.] //
J. Immunol. 2010. Vol. 186. P. 1809–1815.
19. Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inlammation // J. Leukocyte.
Biology. 2007. Vol. 81, issue 3. P. 584–592.
13.10.2014
:
,
:
. .
12
, 650002, .
,
, .6
: +7 (3842) 64-41-56
E-mail: matveeva_vg@mail.ru
Corresponding author:
PhD
Vera G. Matveeva,
senior research associate
of cellular technologies laboratory
of experimental and clinical cardiology
department of NII KPSSZ
Correspondence address:
V. G. Matveeva, 6, Sosnoviy blvd.,
Kemerovo, 650002
Tel.: +7 (3842) 64-41-56
E-mail: matveeva_vg@mail.ru
Скачать