| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-Inducible CXCR3-Binding Chemokines, IFN-Inducible Protein 10, Monokine Induced by IFN, and IFN-Inducible T Cell 
Chemoattractant in Human Cardiac Allografts: Association with Cardiac Allograft Vasculopathy and Acute Rejection1
* Cardiovascular Medicine and Departments of
Cardiac Surgery and
Medicine, Vanderbilt University Medical Center, Nashville, TN 37232;
Center for Immunology and Inflammatory Disease, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and Departments of
¶ Pathology and
|| Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
chemoattractant (I-TAC), monokine induced by
IFN (Mig), and their receptor CXCR3 in consecutive endomyocardial
biopsies (n = 133) from human cardiac allografts
and corresponding normal donor hearts (n = 11)
before transplantation. Allografts, but not normal hearts, contained
IP-10, Mig, and I-TAC mRNA. Persistent elevation of IP-10 and I-TAC was
associated with CAV. Allografts with CAV had an IP-10-GAPDH ratio
3.7 ± 0.8 compared with 0.8 ± 0.2 in those without CAV
(p = 0.004). Similarly, I-TAC mRNA levels were
persistently elevated in allografts with CAV (6.7 ± 1.9 in
allografts with vs 1.5 ± 0.3 in those without CAV,
p = 0.01). In contrast, Mig mRNA was induced only
during rejection (2.4 ± 0.9 with vs 0.6 ± 0.2 without
rejection, p = 0.015). In addition, IP-10 mRNA
increased above baseline during rejection (4.1 ± 2.3 in rejecting
vs 1.8 ± 1.2 in nonrejecting biopsies, p =
0.038). I-TAC did not defer significantly with rejection. CXCR3 mRNA
persistently elevated after cardiac transplantation. Double
immunohistochemistry revealed differential cellular distribution of
CXCR3 chemokines. Intragraft vascular cells expressed high levels of
IP-10 and I-TAC, while Mig localized predominantly in infiltrating
macrophages. CXCR3 was localized in vascular and infiltrating cells.
CXCR3 chemokines are induced in cardiac allografts and differentially
associated with CAV and rejection. Differential cellular distribution
of these chemokines in allografts indicates their central roles in
multiple pathways involving CAV and rejection. This chemokine pathway
may serve as a monitor and target for novel therapies to prevent CAV
and rejection. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
chemoattractant (I-TAC), CXCL11) typically
smaller than 10 kDa and induced by IFN-
. The CXC chemokines fall
into two classes based on the presence or absence of an
NH2-terminal ELR sequence (ELR:
Glu-Leu-Arg). The ELR-containing CXC chemokines (e.g., IL-8) attract
neutrophils, while the non-ELR-containing CXC chemokines (e.g., IP-10,
I-TAC, Mig) attract lymphocytes (1). IP-10, Mig, and I-TAC
bind to their only receptor CXCR3. Activated T cells, NK cells, and
vascular cells express CXCR3. Increased expression of IP-10, Mig, and
I-TAC may contribute to the recruitment and retention of activated T
lymphocytes in conventional atherosclerotic plaques (2, 3). Several studies demonstrate increased expression of various
chemokines in animal transplant models and human transplanted hearts
(4, 5, 6, 7, 8, 9, 10, 11). In murine cardiac transplant models, IP-10 and
its receptor CXCR3 were required for development of rejection (5, 12). Recently, Miura et al. (9) demonstrated that
neutralization of Mig with antiserum prolonged graft survival. These
results indicate significant biological importance of CXCR3 chemokines
in allograft rejection.
The long-term survival of transplanted hearts is limited by CAV.
Increasing evidence supports an immune-mediated and growth
factor-driven mechanism for CAV (13, 14, 15, 16). We and others
have shown that IFN- plays an essential role in the pathogenesis of
CAV (14). Absence or neutralization of IFN- markedly
reduces CAV in mice. IFN- alone sufficed to induce transplantation
arteriosclerosis in SCID mice (17). IFN- modulates the
immune response by stimulating the production of adhesion molecules,
MHC class II expression, and cytokines including CXCR3 chemokines. In
addition to their potent effects on immune system (1),
CXCR3 chemokines potently alter vascular cell functions (3, 18). The dual targets of these molecules suggest a critical role
for these mediators in the pathogenesis of CAV, a disease characterized
by immune-mediated vascular SMC proliferation.
Members of the CXC chemokine family can display disparate angiogenic activity depending upon the presence or absence of the ELR motif. ELR-containing CXC chemokines (e.g., IL-8) stimulate angiogenesis. In contrast, non-ELR-containing CXC chemokines (e.g., platelet factor 4, IP-10, Mig, and I-TAC) are angiostatic (19). Non-ELR-containing CXC chemokines can potentiate growth factor-induced SMC mitogenesis. Cardiac allografts exhibit augmented expression of several growth factors, including acidic fibroblast growth factor, platelet-derived growth factor (20, 21), and vascular endothelial growth factor (22). Increased expression of those growth factors correlates with the development of CAV (15, 16). In contrast, transplanted hearts generally do not develop abundant collateral vessels, despite high levels of angiogenic growth factors (23, 24). Therefore, angiostatic factors such as non-ELR-containing CXCR3 chemokines expressed in the transplanted hearts may antagonize neovessel formation, but promote SMC proliferation. Accordingly, this study tested the hypothesis that expression of CXCR3 chemokines increases in human cardiac allografts and may participate in the pathogenesis of CAV and rejection.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
A total of 133 sequential endomyocardial biopsies from 11 cardiac allografts and biopsies from their corresponding normal donor hearts before the transplantation were analyzed for expression of IP-10, I-TAC, Mig, and CXCR3 mRNA by quantitative RT-PCR. Myocardium from normal donor hearts was obtained before transplantation. Allograft myocardial biopsies were obtained at routine follow-up biopsy after transplantation or when clinically indicated. At each cardiac catheterization, four biopsies were obtained for histology to monitor allograft rejection, and one was obtained and frozen for RNA extraction. Acute allograft rejection was graded according to the criteria established by International Society of Heart Lung Transplantation.
Annual coronary angiography was used to assess CAV. Coronary angiograms were reviewed and compared with baseline angiograms independently by two cardiologists who were unaware of the results of current study. CAV was assessed according to the criteria established by Gao et al. (23).
Isolation of RNA from myocardial biopsies and RT-PCR
Total RNA was isolated from myocardial biopsies using RNAzol B (Tel-Test, Friendswood, TX) and was used as template for cDNA synthesis. Primers used in PCR are IP-10 (5'-agaatgctgtcctcg-3' and 5'-tttcttgcaggctttggtct-3'), Mig (5'-aaatgtaacccaggacgctg-3' and 5'-gccttggatggaagaacaaa-3'), I-TAC (5'-ccactgtccccactgacttt-3' and 5'-ggcaatgacgaaggaggtta-3'), CXCR3 (5'-agctttgaccgctacctgaa-3' and 5'-ctcacaagcccgagtaggag-3'), and GAPDH (24). Techniques of quantitative RT-PCR have been described previously (16, 24). Standard curves within the exponential range of amplification for each gene were generated with known amount of cDNA template. The concentration of cDNA in each sample was calculated from the standards run at the same time. RNA from myocardial biopsies could not be quantitated because of the small size of the biopsies. Therefore, the amount of cDNA for each gene was normalized to the amount of cDNA for GAPDH in each sample. The ratio (x1000) between each gene of interest and GAPDH is used for comparison.
Immunohistochemistry
Biopsies from nine allografts and five normal hearts were analyzed using immunohistochemical staining. Serial cryostat sections (5 µm) were incubated sequentially in 0.3% H2O2/PBS, 5% horse serum/PBS, and first Abs in 5% horse serum/PBS. The primary Abs used were rabbit anti-human IP-10 (1:100), I-TAC (1:50), Mig (1:50) (2, 25, 26), and monoclonal anti-human CXCR3 (R&D Systems, Minneapolis, MN). Rabbit or mouse IgG was used as primary Ab in negative controls at different dilutions (1/30, 1/50, and 1/100), respectively. After wash in PBS, slides were incubated with biotinylated horse anti-rabbit or mouse secondary Ab (Vector Laboratories, Burlingame, CA) and developed using a Vectastain ABC kit (Vector Laboratories) and 3-amino-9-ethyl carbazole substrate kit (Vector Laboratories). For immunofluorescent staining, slides were incubated with streptavidin-conjugated Texas Red (1:100; Amersham, Piscataway, NJ) following secondary Ab. Cell types were determined by double immunofluorescence staining using FITC-labeled cell-specific mAbs, including anti-actin for SMC (DAKO, Carpinteria, CA), anti-CD31 for endothelial cells (EC; DAKO), and anti-CD68 for macrophages (DAKO).
Data analysis
Differences in levels of IP-10, I-TAC, Mig, and CXCR3 mRNA in transplanted hearts were compared in allografts with and without severe CAV, biopsies with and without acute rejection, and normal hearts. Statistical significance was determined by Student’s t test. A value of <0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
We investigated the expression of IP-10, I-TAC, Mig, and CXCR3 in
133 consecutive biopsies from 11 human cardiac allografts (15–17
biopsies for each allograft in a 2-year follow-up) and myocardium
collected from corresponding donor hearts before the transplantation.
Cardiac allografts had high levels of IP-10, I-TAC, and Mig mRNA.
However, none of the 11 normal hearts contained these transcripts
before transplantation (Fig. 1
and Tables I and II). IP-10 mRNA levels correlated well with the development
of CAV (Fig. 2A and Table I). Cardiac
allografts with CAV had persistently elevated
baseline IP-10 mRNA levels. The mean
IP-10-GAPDH ratio (over 2 years) was 3.7 ± 0.8 in patients with
CAV (77 sequential biopsies from six allografts) compared with 0.8
± 0.2 in those without CAV (56 sequential biopsies from five
allografts, p = 0.004). Moreover, IP-10 mRNA further
increased above baseline levels in both CAV and non-CAV groups during
the acute rejection. Of 28 biopsies with rejection, 11 had grade I
(International Society of Heart Lung Transplantation criteria), 17 had
grade II, and 3 had severe rejection (>grade III). The mean
IP-10-GAPDH ratio was 4.1 ± 2.3 in rejecting biopsies (all
grades, n = 28) compared with 1.8 ± 1.2 in
nonrejecting biopsies (n = 105;
p = 0.038, Table II). There were insufficient
numbers of biopsies in each grade to permit a meaningful statistical
analysis of the association between the IP-10 mRNA levels and the
severity of acute rejection. However, accumulation of IP-10 mRNA
increased in both low grade (grade I and II) and high grade (>grade
III) rejection. Fig. 3 shows changes of
IP-10 mRNA levels in a representative patient during rejection
episodes.
|
|
|
|
|
A and Table I). However,
I-TAC levels did not vary substantially during rejection in either the
CAV or the non-CAV group (Figs. 2B and 3 and Table II). Mean
I-TAC-GAPDH ratio was 5.6 ± 1.3 in biopsies with and 4.2 ±
1.2 in those without rejection (p =
NS).
Mig mRNA levels did not elevate persistently and only increased during
acute rejection. Mean Mig/GAPDH levels were 2.4 ± 0.9 in biopsies
with compared with 0.9 ± 0.2 in those without rejection
(p = 0.015, Figs. 2B and 3 and Table II). Levels of Mig mRNA did not differ significantly between CAV vs
non-CAV groups (2.0 ± 1.1 vs 0.98 ± 0.56; p
= NS, Fig. 2A and Table I).
CXCR3 is the common receptor for IP-10, I-TAC, and Mig. CXCR3 mRNA
expressed in normal donor hearts at low levels and increased
immediately after transplantation. All first biopsies from allografts
analyzed in this study contained 3- to 5-folds higher levels of CXCR3
mRNA compared with their corresponding donor hearts before the
transplantation. Mean CXCR3-GAPDH ratio was 1.3 ± 1.0 in first
biopsies after transplantation vs 0.2 ± 0.1 in normal donor
hearts (p < 0.043). CXCR3 mRNA levels remained
persistently elevated in cardiac allografts (Fig. 3). Mean CXCR3-GAPDH
ratio was 0.9 ± 0.7 in all allograft biopsies (2 year follow-up)
vs 0.2 ± 0.1 in normal donor hearts (p <
0.05). CXCR3 levels did not defer significantly during rejection
(Table II).
Cellular distribution of IP-10, I-TAC, Mig, and their receptor CXCR3 in human cardiac allografts
We next localized IP-10, I-TAC, Mig, and CXCR3 protein in human
cardiac allografts by immunohistochemical staining of biopsies from
cardiac allografts and normal hearts. In accordance with the mRNA
results, cardiac allografts demonstrated intense expression of IP-10,
I-TAC, and Mig proteins (Fig. 4, A–C), while normal hearts had negligible levels of those
chemokines (Fig. 4, E–G). Double immunostaining
revealed that vascular SMC contained substantial IP-10 and I-TAC
in cardiac allografts, while vascular EC predominantly expressed I-TAC.
Macrophages expressed all three chemokines. Mig localized predominantly
in macrophages, but not in vascular wall cells (Fig. 5). The receptor CXCR3 primarily
localized in vascular wall cells in cardiac allografts (Fig. 4D).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Although current immunosuppressive regimens have substantially reduced
the incidence of acute allograft rejection, these immunosuppressants do
not prevent CAV. Increasing evidence shows that allograft rejection,
particularly low grade untreated rejection, predisposes cardiac
allografts to CAV (15, 27). CXCR3 chemokines not only
attract leukocytes, but also alter functions of vascular wall cells.
The dual targets of CXCR3 chemokines on immune and vascular cells
suggest an important role for this group of cytokines in CAV, a disease
characterized by immune-mediated vascular smooth muscle cell
proliferation. Current study provides first direct evidence in human
cardiac allografts that persistent elevation of IP-10 and I-TAC is
associated with the development of CAV. Members of the CXC chemokine
family can display disparate angiogenic activity depending upon the
presence or absence of the ELR motif. ELR-containing CXC chemokines
(e.g., IL-8) stimulate angiogenesis. In contrast, non-ELR-containing
CXC chemokines (e.g., platelet factor 4, IP-10, Mig, and I-TAC) are
angiostatic (19). In addition, non-ELR-containing CXC
chemokines can potentiate growth factor-induced SMC mitogenesis.
Transplanted hearts have elevated levels of several growth factors,
which associate with the development of CAV (16, 20, 21, 22).
In contrast, transplanted hearts show scant angiogenesis, despite high
levels of angiogenic growth factors (23, 24). We
originally proposed that mediators produced in transplanted hearts
altered vascular responses to growth factors by inhibiting angiogenesis
and facilitating intimal SMC proliferation (24). Induction
of IP-10, I-TAC, and their receptor CXCR3 in human cardiac allografts,
particularly in vascular SMC, suggests their role in control of SMC
proliferation. Persistent elevation of IP-10 and I-TAC in grafts with
CAV is consistent with the chronic nature of this disease. Moreover,
the presence of non-ELR-containing chemokines (IP-10, I-TAC) may
provide angiostatic effects in transplanted hearts and account for the
absence of angiogenesis in those allografts. Interestingly, Mig only
expresses during rejection and does not elevate persistently as IP-10
and I-TAC do in human cardiac allografts. In addition, Mig is
predominantly expressed in macrophages, but not in donor vascular
cells. The absence of persistent elevation and vascular distribution of
Mig may represent the biological bases for the lack of correlation
between Mig and CAV. Although IP-10, I-TAC, and Mig are IFN-
inducible and share a common receptor (CXCR3), increasing evidence
suggests that their biological functions may differ. Our study provides
new evidence that these CXCR3 chemokines may also be regulated
differently. However, precise mechanisms of differential regulation of
these three CXCR3 chemokines and their biological importance require
further studies.
The development of CAV requires IFN- (14, 17). In this
study, we elucidate the involvement of one set of downstream mediators
of IFN- in CAV and rejection. Thus, the IFN--inducible CXCR3
chemokines most likely recruit T cells to transplanted hearts, and also
alter vascular EC and SMC functions in transplanted hearts. Both
processes can promote the development of CAV. The dual functions of
CXCR3 chemokines in immune and vascular cells make them novel
therapeutic targets for promoting angiogenesis and reducing neointimal
SMC proliferation and rejection in cardiac allografts.
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. David Xiao-Ming Zhao, Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt Medical Center, 2311 Pierce Avenue, PCHI Room 2229, Nashville, TN 37232. E-mail address: david.zhao{at}vanderbilt.edu
3 Abbreviations used in this paper: CAV, cardiac allograft vasculopathy; EC, endothelial cell; I-TAC, IFN-inducible T cell chemoattractant; IP-10, IFN-inducible protein 10; Mig, monokine induced by IFN; SMC, smooth muscle cell.
Received for publication February 22, 2002. Accepted for publication May 20, 2002.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
inducible protein 10 and monokine induced by interferon- in cardiac allografts is mediated by CD8+ T cells. Transplantation 69:1147.[Medline]
is a dominant factor directing T cells into murine cardiac allografts during acute rejection. J. Immunol. 167:3494. deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts. J. Clin. Invest. 100:550.[Medline]
elicits arteriosclerosis in the absence of leukocytes. Nature 403:207.[Medline]
chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J. Exp. Med. 187:2009.This article has been cited by other articles:
|
|
 |
|
  K. Shimizu, M. Minami, R. Shubiki, M. Lopez-Ilasaca, L. MacFarlane, Y. Asami, Y. Li, R. N. Mitchell, and P. Libby CC Chemokine Receptor-1 Activates Intimal Smooth Muscle-Like Cells in Graft Arterial Disease Circulation, November 3, 2009; 120(18): 1800 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Kim, R. Romero, C. J. Kim, A. L. Tarca, S. Chhauy, C. LaJeunesse, D.-C. Lee, S. Draghici, F. Gotsch, J. P. Kusanovic, et al. Villitis of Unknown Etiology Is Associated with a Distinct Pattern of Chemokine Up-Regulation in the Feto-Maternal and Placental Compartments: Implications for Conjoint Maternal Allograft Rejection and Maternal Anti-Fetal Graft-versus-Host Disease J. Immunol., March 15, 2009; 182(6): 3919 - 3927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Shimizu and R. N. Mitchell The Role of Chemokines in Transplant Graft Arterial Disease Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1937 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A Belperio and A. Ardehali Chemokines and Transplant Vasculopathy Circ. Res., August 29, 2008; 103(5): 454 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Borgogni, E. Sarchielli, M. Sottili, V. Santarlasci, L. Cosmi, S. Gelmini, A. Lombardi, G. Cantini, G. Perigli, M. Luconi, et al. Elocalcitol Inhibits Inflammatory Responses in Human Thyroid Cells and T Cells Endocrinology, July 1, 2008; 149(7): 3626 - 3634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schmauss and M. Weis Cardiac Allograft Vasculopathy: Recent Developments Circulation, April 22, 2008; 117(16): 2131 - 2141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Schnickel, S. Bastani, G. R. Hsieh, A. Shefizadeh, R. Bhatia, M. C. Fishbein, J. Belperio, and A. Ardehali Combined CXCR3/CCR5 Blockade Attenuates Acute and Chronic Rejection J. Immunol., April 1, 2008; 180(7): 4714 - 4721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Brainard, A. M. Tager, J. Misdraji, N. Frahm, M. Lichterfeld, R. Draenert, C. Brander, B. D. Walker, and A. D. Luster Decreased CXCR3+ CD8 T Cells in Advanced Human Immunodeficiency Virus Infection Suggest that a Homing Defect Contributes to Cytotoxic T-Lymphocyte Dysfunction J. Virol., August 15, 2007; 81(16): 8439 - 8450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Mitchell and P. Libby Vascular Remodeling in Transplant Vasculopathy Circ. Res., April 13, 2007; 100(7): 967 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tellides and J. S. Pober Interferon-{gamma} Axis in Graft Arteriosclerosis Circ. Res., March 16, 2007; 100(5): 622 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. V. Campanella, J. Grimm, L. A. Manice, R. A. Colvin, B. D. Medoff, G. R. Wojtkiewicz, R. Weissleder, and A. D. Luster Oligomerization of CXCL10 Is Necessary for Endothelial Cell Presentation and In Vivo Activity J. Immunol., November 15, 2006; 177(10): 6991 - 6998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tellides Th1 Adaptive Immune Responses in Cardiac Graft Arteriosclerosis: Deleterious or Beneficial? Circulation, October 10, 2006; 114(15): 1561 - 1564. [Full Text] [PDF]
|
|
|
|
|
|
J. van Loosdregt, M. F.M. van Oosterhout, A. H. Bruggink, D. F. van Wichen, J. van Kuik, E. de Koning, C. C. Baan, N. de Jonge, F. H.J. Gmelig-Meyling, and R. A. de Weger The Chemokine and Chemokine Receptor Profile of Infiltrating Cells in the Wall of Arteries With Cardiac Allograft Vasculopathy Is Indicative of a Memory T-Helper 1 Response Circulation, October 10, 2006; 114(15): 1599 - 1607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Colvin, G. S. V. Campanella, L. A. Manice, and A. D. Luster CXCR3 Requires Tyrosine Sulfation for Ligand Binding and a Second Extracellular Loop Arginine Residue for Ligand-Induced Chemotaxis Mol. Cell. Biol., August 1, 2006; 26(15): 5838 - 5849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Hoffmann, S. Segerer, P. Rummele, B. Kruger, M. Pietrzyk, F. Hofstadter, B. Banas, and B. K. Kramer Expression of the chemokine receptor CXCR3 in human renal allografts--a prospective study Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1373 - 1381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Hardison, R. A. Wrightsman, P. M. Carpenter, T. E. Lane, and J. E. Manning The Chemokines CXCL9 and CXCL10 Promote a Protective Immune Response but Do Not Contribute to Cardiac Inflammation following Infection with Trypanosoma cruzi Infect. Immun., January 1, 2006; 74(1): 125 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zeng, T. A. Moore, M. W. Newstead, J. C. Deng, S. L. Kunkel, A. D. Luster, and T. J. Standiford Interferon-Inducible Protein 10, but Not Monokine Induced by Gamma Interferon, Promotes Protective Type 1 Immunity in Murine Klebsiella pneumoniae Pneumonia Infect. Immun., December 1, 2005; 73(12): 8226 - 8236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Klein, E. Lin, B. Zhang, A. D. Luster, J. Tollett, M. A. Samuel, M. Engle, and M. S. Diamond Neuronal CXCL10 Directs CD8+ T-Cell Recruitment and Control of West Nile Virus Encephalitis J. Virol., September 1, 2005; 79(17): 11457 - 11466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Hauser, S. Spiegler, E. Kiss, S. Gauer, O. Sichler, E. H. Scheuermann, H. Ackermann, J. M. Pfeilschifter, H. Geiger, H.-J. Grone, et al. Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-{gamma} (MIG) J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1849 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Amano, A. Bickerstaff, C. G. Orosz, A. C. Novick, H. Toma, and R. L. Fairchild Absence of Recipient CCR5 Promotes Early and Increased Allospecific Antibody Responses to Cardiac Allografts J. Immunol., May 15, 2005; 174(10): 6499 - 6508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Foley, C.-R. Yu, R. Solow, M. Yacobucci, K. W. C. Peden, and J. M. Farber Roles for CXC Chemokine Ligands 10 and 11 in Recruiting CD4+ T Cells to HIV-1-Infected Monocyte-Derived Macrophages, Dendritic Cells, and Lymph Nodes J. Immunol., April 15, 2005; 174(8): 4892 - 4900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Frangogiannis and M. L. Entman Targeting the Chemokines in Myocardial Inflammation Circulation, September 14, 2004; 110(11): 1341 - 1342. [Full Text] [PDF]
|
|
|
|
|
|
G. C. Hildebrandt, L. A. Corrion, K. M. Olkiewicz, B. Lu, K. Lowler, U. A. Duffner, B. B. Moore, W. A. Kuziel, C. Liu, and K. R. Cooke Blockade of CXCR3 Receptor:Ligand Interactions Reduces Leukocyte Recruitment to the Lung and the Severity of Experimental Idiopathic Pneumonia Syndrome J. Immunol., August 1, 2004; 173(3): 2050 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Segerer, B. Banas, M. Wornle, H. Schmid, C. D. Cohen, M. Kretzler, M. Mack, E. Kiss, P. J. Nelson, D. Schlondorff, et al. CXCR3 Is Involved in Tubulointerstitial Injury in Human Glomerulonephritis Am. J. Pathol., February 1, 2004; 164(2): 635 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. V. Campanella, E. M. J. Lee, J. Sun, and A. D. Luster CXCR3 and Heparin Binding Sites of the Chemokine IP-10 (CXCL10) J. Biol. Chem., May 2, 2003; 278(19): 17066 - 17074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kao, J. Kobashigawa, M. C. Fishbein, W. R. MacLellan, M. D. Burdick, J. A. Belperio, and R. M. Strieter Elevated Serum Levels of the CXCR3 Chemokine ITAC Are Associated With the Development of Transplant Coronary Artery Disease Circulation, April 22, 2003; 107(15): 1958 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-S. Shin, B.-H. Lee, S. Lee, S.-Y. Chung, M. Kim, J. Lim, Y. Kim, H. J. Kwon, C. S. Kang, and K. Han Monokine Levels in Cancer and Infection Ann. Clin. Lab. Sci., April 1, 2003; 33(2): 149 - 155. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
(macrophages), respectively. The green color
indicates positive staining for cell markers indicated. Middle
panels, Staining for chemokines. The red color indicates
positive staining for the respective chemokines. Bottom
panels, Composite double staining with cell markers and
chemokines. The yellow/orange color indicates positive staining for
both cell markers and chemokines.