(Circulation. 1995;92:315-321.)
© 1995 American Heart Association, Inc.
Articles |
Induction of Interleukin-8 Messenger RNA in Heart and Skeletal Muscle During Pediatric Cardiopulmonary Bypass
From the Departments of Cardiology, Cardiac Surgery (J.E.M.) and Anesthesia (M.X.), and the Division of Hematology (E.J.N.), Children's Hospital, Dana Farber Cancer Institute, and the Departments of Pediatrics and Cardiovascular Surgery, Harvard Medical School, Boston, Mass.
Correspondence to Ellis J. Neufeld, MD, PhD, Hematology Research, Children's Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail neufeld@a1.tch.harvard.edu.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Interleukin-8 (IL-8), the major neutrophil chemoattractant factor, contributes to inflammatory tissue injury by activating neutrophils and promoting their migration into tissue. IL-8 levels increase in serum of patients undergoing cardiopulmonary bypass (CPB). The purpose of this study was to determine if IL-8 gene expression is activated in tissues subjected to CPB with or without hypothermic arrest.
Methods and Results IL-8 transcript levels were measured by ribonuclease protection in samples of human atrium and skeletal muscle from children before and after CPB for repair of congenital heart defects. Results were quantified by PhosphorImager. Atrial IL-8 mRNA levels increased during CPB in 14 of 16 patients tested (median increase, 2.9-fold; P=.0029). In skeletal muscle, IL-8 mRNA increased in 11 of 12 patients (median, 12-fold; P=.012). Degree of IL-8 induction in atrium and muscle was not directly associated with total support time or cross-clamp time. Transcript increase in skeletal muscle occurred with or without a period of circulatory arrest, suggesting that the stimulus of CPB alone was sufficient to induce message production. Baseline values for IL-8 mRNA varied widely among patients in atrium and skeletal muscle. In situ hybridization analysis revealed diffuse increase in IL-8 mRNA throughout the tissue after CPB, with striking increase in some small veins.
Conclusions We conclude that production of IL-8 mRNA occurs in most patients during CPB in both myocardium and skeletal muscle. This may result in high local IL-8 concentrations, contributing to the tissue injury after CPB.
Key Words: interleukins • muscles • bypass
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
The use of CPB induces a "whole body inflammatory reaction" accompanied by postoperative morbidity.1 2 Generalized edema as a result of capillary leak is particularly common in pediatric patients.3 The exact mechanisms of injury of CPB are incompletely understood. The complex pathophysiology involves at least two kinds of injury: (1) activation of leukocytes and inflammatory cascades in the extracorporeal circuit1 4 5 6 7 and (2) ischemia-reperfusion of the heart and lungs or of the entire body in the case of DHCA.8 The neutrophil appears to be an essential mediator for tissue damage related to CPB and ischemia-reperfusion injury.8 9 10 Accumulation of neutrophils at sites of injury is the result of a multistep process; circulating neutrophils are attracted to the region of injury, adhere to the endothelium, and migrate into the tissue in response to local induction of adhesion molecules and chemoattractants.11 12
IL-8, also known as monocyte-derived neutrophil chemoattractant factor and neutrophil-activating factor, is a ubiquitous neutrophil-specific chemoattractant implicated in inflammation in diverse diseases.13 14 15 IL-8 is produced by monocytes, endothelial cells, and several other cell types.13 In vitro, regulation of IL-8 synthesis occurs at the level of transcription, with increased levels of specific mRNA noted within 1 hour of stimulation of cultured cells by LPS, TNF, or IL-1.13 16
IL-8 levels are increased in blood in the setting of CPB both in adult17 18 19 and pediatric20 21 22 patients; the sites of synthesis, however, have not been determined. To gain a clearer understanding of the regulation of IL-8 expression in vivo, we examined IL-8 mRNA levels at the tissue level in atrial and skeletal muscle from pediatric patients undergoing CPB and cardiac surgery.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Subjects
Twenty-six pediatric patients undergoing cardiac surgery for repair or palliation of a variety of congenital structural lesions were enrolled in the study. Selection criteria included (1) no recent intracardiac operations, (2) no known preexisting vascular disease, (3) informed consent of the parents, and (4) post-CPB tissue obtained by the surgeon. The study protocol was approved by the Committee for Clinical Investigation at Children's Hospital. Patients ranged in age from 3 days to 6
years.
Surgical Technique
Hypothermic CPB was used in all patients.
All patients received
methylprednisolone 30 mg/kg before onset of bypass. Patients were
cooled with ice bags and cooling blankets while being prepared for CPB.
Cannulas were inserted in the ascending aorta and right atrium, and
core cooling was begun with bypass. A membrane oxygenator (Cobe VPCML,
Cobe Cardiovascular) was used in all cases. In DHCA
cases, hemodilution to achieve a hematocrit of 0.20 was accomplished
with Plasma-Lyte (Baxter Healthcare) as the priming solution for the
oxygenator. The aorta was cross-clamped, and cold (4°C)
cardioplegia solution (Plegisol, Abbott Laboratories) was infused into
the aortic root. In patients who required total circulatory arrest,
perfusion was discontinued when the core temperature reached 18°C and
the patient's blood was drained into the pump reservoir. When the
intracardiac portions of the procedures were completed, the aortic
cross-clamp was removed and the patient was rewarmed during
bypass.
Intraoperative parameters were recorded for each patient. These included total support time, including duration of CPB plus DHCA, aortic cross-clamp time (duration of myocardial ischemia), and duration of DHCA (and consequent whole body ischemia).
Specimen Collection and Analysis
Specimens were collected in
a manner similar to that previously
described.23 Briefly, samples of atrium and skeletal
muscle were obtained just before onset of CPB and again after
reperfusion at the conclusion of the surgical procedure. Specimens were
snap-frozen in liquid nitrogen and stored at -80°C until use.
For in situ hybridization, specimens were put immediately into 4%
paraformaldehyde for 3 to 6 hours, then into 30%
sucrose overnight, drained, and frozen at -80°C.
Frozen tissue samples for RNA analysis were pulverized with the use of a Bessman steel piston apparatus (VWR). Total RNA was extracted using a phenol-guanidinium-SCN method24 with RNAzol B (Cinna/Biotecx). Quantification of total RNA, resuspended in 0.5% sodium dodecyl sulfate, was by spectrophotometry.
cDNA
templates of human IL-8 and 
-actin were chosen to be of
different lengths to allow multiplex RNase protection analysis.
The IL-8 probe was 274 nucleotides with the protected
sequence 253 bp in length, from bp 99 to 351 in the full-length
cDNA.25 The selected fragment of IL-8 cDNA was amplified
by polymerase chain reaction from full-length cDNA kindly provided
by Genentech, South San Francisco, Calif. Restriction sites were
incorporated into the primers to facilitate cloning. The fragment was
cloned into the BamHI and Kpn sites of
pBluescript II SK (Stratagene; La Jolla, Calif).
All riboprobes were
synthesized by runoff transcription with the
appropriate viral RNA polymerase. RNA from HUVEC stimulated with
TNF-
was prepared as described.23 One milligram of
HUVEC RNA was used as a positive control. For each patient-specimen
pair (before and after CPB), equal amounts of RNA were analyzed
in parallel. Ten micrograms of yeast tRNA was used as a negative
control in each experiment. All samples were simultaneously
hybridized with IL-8 and -actin26 27 probe. The
latter served as internal control for recovery. RNase protection and
electrophoretic analysis were performed as
described.23
Signals were quantified with the use of
IMAGEQUANT software
after 24-hour exposure to PhosphorImager screens (Molecular Dynamics).
Normalization for -actin recovery was performed with the
following formula: [(IL-8 mRNA-background)/(-actin
mRNA-background)]post-CPB/[(IL-8
mRNA-background)/(-actin
mRNA-background)]pre-CPB.
In Situ Hybridization
Templates for IL-8 riboprobes were
those used for RNase
protection as above and were prepared as described23
except that [35S]--UTP was used for
radiolabel, and the nucleotide concentration was CTP, GTP,
and ATP, 0.5 mmol/L; unlabeled UTP, 1.2 µmol/L. In situ hybridization
was performed following the protocol from Hoefler et al.28
Fixed tissue specimens were embedded in OCT compound (Miles
Laboratories, Inc), then 8-µm sections were cut onto
gelatin-coated or Super Frosted slides (Fisher Scientific). After
prehybridization,28 the tissue section slides were
drained, and hybridization mixture, which contained 3x105
cpm 35S-labeled antisense or sense RNA probe and
hybridization buffer (50% formamide, 2xSSC, 10% dextran sulfate,
0.25% bovine serum albumin, 0.25% Ficoll 400, 0.25%
polyvinyl-pyrrolidine 360, 0.5% sodium dodecyl sulfate,
and 250 µg/mL denatured salmon sperm DNA), on each slide. Tissue
sections were incubated at 42°C for 16 hours and washed four times
for 15 minutes each in 4xSSC at 42°C. RNase A digestion (10
µg/mL
for 30 minutes) was followed by removal of salt from the section and
dehydration in graded alcohol solutions containing 0.3 mol/L ammonium
acetate. Autoradiography was performed by dipping
the tissue section slides in NTB2 emulsion (Kodak) diluted 1:2 with
water. After developing, sections were stained with hematoxylin and
eosin.
Statistical Analysis
We performed paired t tests on
log-transformed
values to compare ratios (ie, log [IL-8 post/IL-8 pre]=log
[IL-8
post]-log [IL-8 pre]). Normalized values between 0 and 1
were
assumed to be 1 before log transformation. Correlation analysis
was used to compare the relationship of IL-8 mRNA levels and clinical
variables. Probability values <.05 were considered to be
significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
The patient diagnoses and surgical procedures are summarized in the Table
. Of the 26 patients studied, there were no
intraoperative deaths. The duration of intraoperative total support
time for the group ranged from 40 to 196 minutes (median, 104 minutes).
Aortic cross-clamp time ranged from 0 to 121 minutes (median, 60
minutes). Eleven patients had a period of DHCA (median duration, 38
minutes; range, 1 to 72 minutes). Tissue samples were not large enough
to use both for RNase protection and in situ analysis.
Therefore, 7 patients (ID Nos. 102 through 108) had tissue used only
for in situ hybridization and not for quantitation. After surgery, 15
of the 19 patients whose IL-8 mRNA levels were studied by RNase
protection had uncomplicated initial recovery periods, spending 6 or
less days in the intensive care unit. There was one death within 24
hours of the surgical procedure (ID No. 71 with hypoplastic left heart
syndrome).
|
Multiplex RNase protection assays demonstrated distinct bands for IL-8
and -actin transcripts in control HUVEC RNA (Fig 1).
Baseline (pre-CPB) levels of IL-8 mRNA were just
above background in 1 of 16 atrial muscle specimens and in 4 of 12
skeletal muscle specimens. Of note, the baseline amounts of IL-8 mRNA
differed widely from patient to patient in both tissues (Figs 2
and 3). RNase protection results are not
readily converted to absolute amounts of mRNA product. A rough
gauge of IL-8 message induction can be inferred from Fig 1,
comparing
atrial samples with TNF-–stimulated HUVEC RNA. The
-actin control signals from 8 µg atrial tissue are slightly
less than that seen in 1 µg pure endothelial cells.
The IL-8 atrial signals range from much less than the HUVEC lane to
substantially greater (for example, Fig 1, ID No. 19 versus ID
No. 24).
Also, -actin recovery was consistent within pairs, but
there was some variability among pairs. This reflects uncertainty in UV
absorption quantitation of tiny amounts of total RNA. We corrected for
this variability by normalizing reported IL-8 values for -actin
signal.
|
|
|
IL-8 message increased in post-CPB samples of atrium from 14 of 16
patients (examples of raw data are shown in Fig 1
, normalized
counts in
Fig 2, and ratios in the Table). Induction in
atrial specimens varied
widely, ranging from 1.1- to 270-fold (median, 2.9-fold;
P=.0029). In 2 patients, ID No. 83 and ID No. 27 in the
Table, the amount of IL-8 transcript decreased slightly after
CPB.
In skeletal muscle, IL-8 mRNA increased in 11 of 12 patients, with a
median increase of 12-fold (range, 1.0; no change) to 63 000-fold
(P=.012, Fig 3 and Table). Of
the 12 patients from whom
skeletal muscle samples were examined, 5 underwent a period of DHCA.
Duration of DHCA among these patients ranged from 26 to 72 minutes
(median, 43 minutes). As in the atrium, induction varied widely,
differing from one patient to another by several logs. Greatest
induction in skeletal muscle was not necessarily associated with
greatest induction in atrium in the 9 patients for whom both were
studied. For neither atrial nor skeletal muscle was the degree of IL-8
induction significantly associated with total support time, aortic
cross-clamp time, patient age, days in the intensive care unit,
days of mechanical ventilation, or preoperative presence of
cyanosis.
Because many cell types are capable of producing IL-8, we used in situ
hybridization to evaluate the distribution of IL-8 mRNA in tissue
samples before and after CPB. We predicted that this would allow us to
distinguish between the possibilities of (1) infiltration of
mononuclear cells causing the observed increase in IL-8 transcript, (2)
strictly vascular production, or (3) diffuse production
of IL-8 mRNA in the muscle parenchyma. The results of the studies are
shown in Fig 4. There was a marked increase in grains
diffusely over the atrial tissue after bypass in the majority of
sections examined. (Fig 4A and 4B, before CPB,
versus 4C and 4E, after
CPB). In general, the label was not associated only with vessels but
covered the entire parenchyma. The grains observed were not associated
with substantial inflammatory infiltrate either of mononuclear cells or
granulocytes (Fig 4B, 4D, and 4F;
light micrographs). However, a subset
of veins in the tissue was strikingly labeled, implying strong
induction of IL-8 mRNA (white arrows in Fig 4C and
4E, with
corresponding structures in Fig 4D and 4F). On
the other hand, several
small veins in the same tissue sections (arrowheads, Fig 4E)
were not
strongly labeled. Control sections labeled with sense IL-8 probe had
essentially no grains (Fig 4G). Similar in situ hybridization
results
were observed in skeletal muscle (photomicrographs not shown). In two
of three skeletal muscle samples from patients exposed to CPB and DHCA
(ID Nos. 102, 104, and 106 in the Table) for 19 to 56 minutes,
there
was marked diffuse increase in grains over the tissue, while in one the
level was unchanged. Of 4 patients whose skeletal muscle was not
ischemic (CPB without DHCA), 1 (ID No. 108) had a clear
increase in grain density, 2 were not substantially changed, and 1
appeared to decrease after CPB. We conclude that the muscle parenchyma
is responsible for much of the observed IL-8 mRNA production
after CPB/reperfusion. A subset of highly induced veins also
contributes to the transcript level in some regions.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Tissue injury after CPB is a complex series of events with multiple mediators. IL-8, a potent and selective chemoattractant for neutrophils, is of particular interest in CPB-related inflammation because neutrophils are implicated in the pathogenesis of tissue injury. We examined the local regulation of IL-8 mRNA by using atrial and skeletal muscle samples from pediatric patients undergoing CPB. Because the human specimens are necessarily small, we used a sensitive RNase protection assay to demonstrate increased IL-8 mRNA production with CPB. To our knowledge, this is the first report of human cardiac IL-8 mRNA production in vivo. A recent report by Kukielka et al29 examined IL-8 production in ischemic/reperfused canine myocardium with experimental myocardial infarction. Northern blots revealed induction of IL-8 mRNA within 3 hours of reperfusion but none during the ischemic period. Immunohistochemical staining revealed IL-8 on the luminal face of vessels and between cardiac myocytes, but the cell of synthesis could not be determined with these studies. These authors noted a subset of veins with marked histochemical staining of IL-8, as did we, for mRNA in the present study (Fig 4C
and
4E). Several investigators have reported elevated circulating levels of IL-8 protein measured in adult and pediatric patients undergoing CPB.17 18 19 20 21 22 In adult patients, transiently increased levels of IL-8 protein in blood and peripheral blood monocytes are seen during and immediately after CPB.17 18 19 Kawamura et al19 demonstrated a linear correlation between serum IL-8 and plasma elastase, a neutrophilic granule enzyme, suggesting that neutrophil activation may have been caused by IL-8. Pediatric patients also have a transient rise in IL-8 plasma levels beginning at the time of rewarming and peaking 1 to 3 hours after CPB, with wide interpatient variability in the absolute amount of IL-8.20 Finn et al20 noted a linear correlation between IL-8 concentration and the length of CPB. These observations demonstrate that IL-8 is present in the circulation around the time of CPB but do not address the induction of IL-8 production in cardiac or peripheral tissue. Neutrophil chemotactic activity has been noted in coronary sinus effluent of adults undergoing CPB; the investigators concluded that the myocardium was the source of the chemotactic factor.30 This chemotactic activity was retained after filtration through a membrane with molecular weight cutoff of 300 kD and was, therefore, unlikely to be free IL-8, which has a molecular weight of 8 kD.25
The source of circulating IL-8 in CPB is not known. In vitro, many cell
types have been shown to synthesize IL-8, including monocytes and
endothelial cells.13 In cultured
endothelial cells, baseline levels of IL-8 mRNA or
protein are not detectable, yet with appropriate stimulation (IL-1,
TNF, or LPS), IL-8 mRNA is detected as early as one-half hour after
the stimulus.16 Our data are consistent with this
time course. For example, dramatic IL-8 mRNA induction occurred in one
patient (ID No. 63, Table) in both atrium (16-fold) and
skeletal muscle
(1400-fold) after only 40 minutes of total support time (no circulatory
arrest) and 17 minutes of aortic cross-clamp time. However, in
another patient (ID No. 83) with similar support times (42 minutes of
total support time, 16 minutes of aortic cross-clamp time, no
circulatory arrest), atrial mRNA levels fell slightly after CPB while
muscle IL-8 mRNA increased 9.8-fold. These results emphasize the
complexity and variability of the patient inflammatory response to CPB.
Karakurum et al31 have reported that hypoxia alone
can induce IL-8 gene expression in HUVEC, but this response is slower
than that observed in patients, taking 6 to 16 hours rather than a
fraction of an hour after CPB.
Two potential sources of IL-8 during CPB are (1) tissues exposed to
inflammatory mediators and/or ischemia/reperfusion and (2)
leukocytes activated in the extracorporeal circulation. Our
results demonstrate that the tissues produce IL-8, which will play a
local and possibly systemic inflammatory role. Our in situ studies
clearly show that IL-8 is produced in the parenchyma of the tissue, not
solely by invading inflammatory cells. Cellular sources of IL-8 mRNA
might include endothelium or myocytes. The resolution
of in situ hybridization by [35S]-labeled
riboprobe and overlying emulsion grains is not fine enough to be
certain whether the smallest capillaries or the myocytes themselves
make the majority of observed signal, although we suspect that myocytes
contribute, based on numerous high-power fields examined (data not
shown). In some segments of tissue, small veins were very prominently
stained, but not in others. Histological studies,
including high-power views of bright-field micrographs as in
Fig 4D and 4F, do not suggest substantial
inflammatory cellular
infiltrate at the early times we have examined (data not shown). This
is not surprising, since inflammatory infiltrates in grossly
ischemic myocardium come substantially later than
the 20- to 60-minute postischemia sample points taken in
these studies.29
Cardiac tissue is subjected to ischemia whenever an aortic
cross-clamp is applied in CPB and/or DHCA occurs (all of our
patients except ID No. 68). Skeletal muscle, however, is constantly
perfused during CPB except in the case of DHCA. Thus, comparison of
skeletal muscle IL-8 induction with or without DHCA should help
distinguish induction caused by ischemia-reperfusion from
induction caused by CPB alone. IL-8 transcript induction was not
greater in patients experiencing a period of DHCA (Table),
suggesting
that CPB was sufficient stimulus to induce message
production.
Of note in our findings was the variation among patients (by several
orders of magnitude) in the degree of induction of IL-8 mRNA observed
both in atrial and skeletal muscle. In addition, we noted wide
variation in the baseline levels of IL-8 transcript. Although IL-8
induction was not related to clinical parameters such as
total support time, aortic cross-clamp time, circulatory arrest
time, or patient age, we had insufficient power to exclude such
associations given our small number of patients. Because the human
tissue samples are necessarily very small, it is possible that the
variation from patient to patient observed in the Table and
Figs 2 and 3 reflects variation in number of
veins in the postbypass sample rather
than physiological differences. To investigate this
possibility, studies are under way in a lamb model of
cardiopulmonary bypass (where tissue amount is not a
limiting factor). Furthermore, the heterogeneity of
cardiac lesions among the patients studied (reflecting the complex mix
of cardiac lesions seen at this center and among pediatric patients
with congenital heart disease) may have been responsible, in part, for
the variability in IL-8 mRNA response observed. Variability in IL-8
protein levels in a similarly heterogeneous group of
pediatric patients20 is greater than that described in
adults undergoing CPB.17 18 19
Summary
Our data demonstrate local IL-8 mRNA production in
cardiac
and skeletal muscle, which is likely to result in high local
concentrations of IL-8. We postulate that this local cytokine
release augments neutrophil recruitment and contributes to subsequent
tissue damage in some patients. Further elucidation of in vivo IL-8
regulation may help direct investigation of potential therapeutic
strategies to ameliorate post-CPB morbidity in children undergoing
CPB.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This work was supported by National Institutes of Health grants HL-48675 and DK-01977.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Kirklin JW, Barratt-Boyes BG. Cardiac Surgery. 2nd ed. New York, NY: Churchill Livingstone; 1993:9999.
2. Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg.. 1993;55:552-559. [Abstract]
3. Brans YW, Dweck HS, Harris HB, Parr GVS, Bailey PE, Kirklin JW, Cassady G. Effect of open-heart surgery on the body composition of infants and young children. Pediatr Res.. 1981;15:1024-1028. [Medline] [Order article via Infotrieve]
4.
Wachtfogel YT, Kucich U, Greenplate J, Gluszko P,
Abrams W, Weinbaum G, Wenger RK, Rucinski B, Niewiarowski S, Edmunds LH
Jr, Colman RW. Human neutrophil degranulation during
extracorporeal circulation. Blood. 1987;69:324-330.
5. Faymonville ME, Pincemail J, Duchateau J, Paulus JM, Adam A, Deby-Dupont G, Deby C, Albert A, Larbuisson R, Limet R, et al. Myeloperoxidase and elastase as markers of leukocyte activation during cardiopulmonary bypass in humans. J Thorac Cardiovasc Surg. 1991;102:309-317. [Abstract]
6. Hind CR, Griffin JF, Pack S, Latchman YE, Drake HF, Jones HM, Brostoff J, Dormandy TL, Treasures T. Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity. Cardiovasc Res.. 1988;22:37-41. [Medline] [Order article via Infotrieve]
7. Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med.. 1981;304:497-503. [Abstract]
8. Breda MA, Drinkwater DC, Laks H, Bhuta S, Corno AF, Davtyan HG, Chang P. Prevention of reperfusion injury in the neonatal heart with leukocyte-depleted blood. J Thorac Cardiovasc Surg. 1989;97:654-665. [Abstract]
9.
Dreyer WJ, Michael LH, West MS, Smith CW, Rothlein R,
Rossen RD, Anderson DC, Entman ML. Neutrophil accumulation in
ischemic canine myocardium.
Circulation. 1991;84:400-411.
10.
Romson JL, Hook BG, Kunkel SL, Abrams GD, Schork MA,
Lucchesi BR. Reduction of the extent of ischemic
myocardial injury by neutrophil depletion in the dog.
Circulation. 1983;67:1016-1023.
11. Elliott MJ, Finn AHR. Interaction between neutrophils and endothelium. Ann Thorac Surg. 1993;56:1503-1508. [Abstract]
12.
Carlos TM, Harlan JM.
Leukocyte-endothelial adhesion
molecules. Blood.. 1994;84:2068-2101.
13. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989;84:1045-1049.
14. Smith WB, Gamble JR, Clark-Lewis I, Vadas MA. Interleukin-8 induces neutrophil transendothelial migration. Immunology. 1991;72:65-72. [Medline] [Order article via Infotrieve]
15.
Huber AR, Kunkel SL, Todd RF 3rd, Weiss SJ.
Regulation of transendothelial neutrophil
migration by endogenous interleukin-8 [published errata
appear in Science. 1991 Nov 1;254(5032):631 and 1991 Dec
6;254(5037):1435]. Science.. 1991;254:99-102.
16.
Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH,
Ward PA, Marks RM. Endothelial cell gene
expression of a neutrophil chemotactic factor by TNF-A, LPS, and
IL-1B. Science. 1989;243:1467-1469.
17. Jorens PG, De Jongh R, De Backer W, Van Damme J, Van Overveld F, Bossaert L, Walter P, Herman AG, Rampart M. Interleukin-8 production in patients undergoing cardiopulmonary bypass: the influence of pretreatment with methylprednisolone. Am Rev Respir Dis.. 1993;148:890-895. [Medline] [Order article via Infotrieve]
18. Kalfin RE, Engelman RM, Rousou JA, Flack JE, Deaton DW, Kreutzer DL, Das DK. Induction of interleukin-8 expression during cardiopulmonary bypass. Circulation. 1993;88:401-406.
19. Kawamura T, Wakusawa R, Okada K, Inada S. Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. Can J Anaesth. 1993;40:1016-1021. [Medline] [Order article via Infotrieve]
20. Finn A, Naik S, Klein N, Levinsky RJ, Strobel S, Elliot M. Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg.. 1993;105:234-241. [Abstract]
21. Finn A, Moat N, Rebuck N, Klein N, Strobel S, Elliott M. Changes in neutrophil CD11b/CD18 and L-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass. Agents Actions. 1993;38:C44-C46.
22. Millar AB, Armstrong L, van der Linden J, Moat N, Ekroth R, Westwick J, Scallan M, Lincoln C. Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg.. 1993;56:1499-1502. [Abstract]
23.
Kilbridge PM, Mayer JE, Newburger JW, Hickey PR, Walsh
AZ, Neufeld EJ. Induction of ICAM-1 and E-selectin mRNAs in
heart and skeletal muscle of pediatric patients undergoing
cardiopulmonary bypass. J Thorac
Cardiovasc Surg.. 1994;107:1183-1192.
24. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium-thiocyanate-phenol-chloroform extraction. Anal Biochem.. 1987;162:156-159. [Medline] [Order article via Infotrieve]
25.
Matsushima K, Morishita K, Yoshimura T, Lavu S,
Kobayashi Y, Lew W, Appella E, Kung HF, Leonard EJ, Oppenheim JJ.
Molecular cloning of a human monocyte-derived neutrophil
chemotactic factor (MDNCF) and the induction of MDNCF mRNA by
interleukin-1 and tumor necrosis factor. J Exp
Med. 1988;167:1883-1893.
26.
Enoch T, Zinn K, Maniatis T. Activation of the
human beta-interferon gene requires an interferon-inducible
factor. Mol Cell Biol. 1986;6:801-810.
27.
Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes
L. Isolation and characterization of full-length cDNA clones
for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not
cytoplasmic actins have an amino-terminal cysteine that is
subsequently removed. Mol Cell Biol.. 1983;3:787-795.
28. Hoefler H, Childers H, Montminy MR, Lechan RM, Goodman RH, Wolfe HJ. In situ hybridization methods for the detection of somatostatin mRNA in tissue sections using antisense RNA probes. Histochem J.. 1986;18:597-604. [Medline] [Order article via Infotrieve]
29. Kukielka GL, Smith CW, LaRosa GJ, Manning AM, Mendoza LH, Daly TJ, Hughes BJ, Youker KA, Hawkins HK, Michael LH, Rot A, Entman ML. Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vitro. J Clin Invest. 1995;95:89-103.
30. Elgebaly SA, Hashmi FH, Houser SL, Allam ME, Doyle K. Cardiac-derived neutrophil chemotactic factors: detection in coronary sinus effluents of patients undergoing myocardial revascularization. J Thorac Cardiovasc Surg.. 1992;103:952-959. [Abstract]
31. Karakurum M, Shreeniwas R, Chen J, Pinsky D, Yan S-D, Anderson M, Sunouchi K, Major J, Hamilton T, Kuwabara K, Rot A, Nowygrod R, Stern D. Hypoxic induction of interleukin-8 gene expression in human endothelial cells. J Clin Invest. 1994;93:1564-1570.
This article has been cited by other articles:
 |
|
 |
|
  R. Lango, L. Anisimowicz, J. Siebert, J. Rogowski, A. Bakowska, P. Mrozinski, and M. Narkiewicz IL-8 concentration in coronary sinus blood during early coronary reperfusion after ischemic arrest Eur. J. Cardiothorac. Surg., September 1, 2001; 20(3): 550 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wan and A. P.C. Yim Cytokines in myocardial injury: impact on cardiac surgical approach Eur. J. Cardiothorac. Surg., September 1, 1999; 16(suppl_1): S107 - S111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E John, J. Galea, S. E Francis, C. M Holt, and A. Finn Interleukin-8 mRNA expression in circulating leucocytes during cardiopulmonary bypass Perfusion, December 1, 1998; 13(6): 409 - 417. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Wan, J.-L. LeClerc, and J.-L. Vincent Cytokine Responses to Cardiopulmonary Bypass: Lessons Learned From Cardiac Transplantation Ann. Thorac. Surg., January 1, 1997; 63(1): 269 - 276. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||