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Biomedical subjects

M Takeya

Publications and source records attributed to M Takeya.

At least 55 records · Page 3Linked to original sources
PubMed1998

Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia-reperfusion of the liver in rats.

Intercellular adhesion molecule-1 (ICAM-1) is important in neutrophil-dependent injury. We investigated the effects of monocyte chemoattractant protein-1 (MCP-1) produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion in rat liver by occluding the portal vein for 30 minutes. Serum concentrations of MCP-1 increased persistently. By Northern analysis, MCP-1 mRNA increased early and persisted. Kupffer cells harvested 6 hours after reperfusion also expressed this transcript. The transcript and protein also were produced by Kupffer cells from naive controls in response to reactive oxygen species. ICAM-1 mRNA transcripts increased, peaked 3 hours after reperfusion, and decreased gradually thereafter. The level of ICAM-1 mRNA transcripts in the WK-5 rat endothelial cell line were markedly enhanced by MCP-1. These results suggest that MCP-1 released by Kupffer cells early after ischemia-reperfusion modulates neutrophil-dependent tissue injury via ICAM-1.

Animals↗
PubMed1998

Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver.

Arginine is a precursor for the synthesis of urea, polyamines, creatine phosphate, nitric oxide and proteins. It is synthesized from ornithine by argininosuccinate synthetase and argininosuccinate lyase and is degraded by arginase, which consists of a liver-type (arginase I) and a non-hepatic type (arginase II). Recently, cDNAs for human and rat arginase II have been isolated. In this study, immunocytochemical analysis showed that human arginase II expressed in COS-7 cells was localized in the mitochondria. Arginase II mRNA was abundant in the rat small intestine and kidney. In the kidney, argininosuccinate synthetase and lyase were immunostained in the cortex, intensely in proximal tubules and much less intensely in distal tubules. In contrast, arginase II was stained intensely in the outer stripes of the outer medulla, presumably in the proximal straight tubules, and in a subpopulation of the proximal tubules in the cortex. Immunostaining of serial sections of the kidney showed that argininosuccinate synthetase and arginase II were colocalized in a subpopulation of proximal tubules in the cortex, whereas only the synthetase, but not arginase II, was present in another subpopulation of proximal tubules. In the liver, all the enzymes of the urea cycle, i.e. carbamylphosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase and lyase and arginase I, showed similar zonation patterns with staining more intense in periportal hepatocytes than in pericentral hepatocytes, although zonation of ornithine transcarbamylase was much less prominent. The implications of these results are discussed.

Animals↗
PubMed1998

Morphological alteration of cultured tracheobronchial epithelial cells is accompanied by the expression of chemokines, MCP-1 and CINC/gro, in rats.

Morphologically altered epithelial cells are generally observed in fibrotic lung conditions and have been reported to produce several cytokines. To examine the relationship between morphological changes of the tracheobronchial epithelial cells (TBECs) and their chemokine production, we investigated, (1) the mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant/gro (CINC/gro), (2) morphological changes by electron microscopy, and (3) cytokeratin (CK) expression, using a primary culture system of rat TBECs. The constitutive secretion of MCP-1 in the culture supernatant of TBECs increased in a time-dependent manner, whereas the CINC/gro secretion was not changed. These results were consistent with the chemokines' mRNA expression observed by in situ hybridization. The constitutive secretions of MCP-1 and CINC/gro were inhibited partially but significantly by dexamethasone. With the extension of the culture period, the morphology of the TBECs became flat and spindle in shape, similar to squamous metaplasia, as observed on electron microscopy, and with strong expression of CK 14. Sequential staining using immunocytochemistry and in situ hybridization revealed the coexpression of MCP-1 mRNA and CK 14. These data indicate a significant relationship between the morphological squamoid alteration and the constitutive expression of MCP-1 but not of CINC/gro. It is thought that the squamous metaplasia of TBECs may accompany the alteration of cytokine production and play an important role in chronic lung inflammation.

Animals↗
PubMed1998

Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentiation of blood monocytes in rat skin.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for blood monocytes in vitro. Recent studies in MCP-1-transgenic mice revealed that the local production of MCP-1 caused monocyte infiltration. However, the kinetics of monocyte infiltration after the production of MCP-1 or the amount of MCP-1 necessary for monocyte recruitment are not known. METHODS: We purified recombinant rat MCP-1 expressed in COS-7 cells, and injected it into rat skin. The infiltrating cells were examined by immunohistochemistry and ultrastructural peroxidase cytochemistry. RESULTS: Rat recombinant MCP-1 had a molecular mass of approximately 30 kD and exhibited the peak monocyte chemotactic activity at 10(-9) M. One microgram of MCP-1 caused intra- and extravascular accumulation of mononuclear cells 3 h after injection. The cells were ED1+, indicating they were blood monocytes. The infiltration of mononuclear cells peaked at 12-24 h, and most of them were TRPM-3+ and ED3+, characteristic to exudate macrophages. None of the cells expressed ED2 or Ki-M2R antigens, markers for resident macrophages, until 3 days after injection. There was no uptake of [3H]thymidine by the infiltrating cells. Ultrastructural peroxidase cytochemistry confirmed that the infiltrating cells were monocytes and exudate macrophages. The number of OX8+ lymphocytes also peaked at 12 h, consisting of approximately 9% of the total infiltrating cells. CONCLUSION: These results indicate that MCP-1 attracts blood monocytes as early as 3 h and the infiltrating monocytes differentiate into exudate macrophages in loco. However, this effect was transient and the infiltration of monocytes did not result in tissue damage.

Animals↗
PubMed1998

Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels.

We recently showed that chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (alpha-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP-1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later-stage structural changes observed in rat hearts.

Animals↗
PubMed1998

Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice.

To clarify the role of type I and type II macrophage scavenger receptors (MSR-A) in the progression of diet-induced atherosclerosis, we generated mice lacking both MSR-A and low-density lipoprotein receptor (LDLR). After 4 or 12 weeks of a high-fat diet, the sizes of atherosclerotic lesions in MSR-A/LDLR double knockout mice were significantly reduced (p < 0.05) compared with those in LDLR single knockout mice. However, atherosclerotic lesions mainly composed of foamy macrophages were still observed in double knockout mice. Formation of atherosclerotic lesions in double knockout mice was partially explained by the participation of scavenger receptors other than MSR-A such as MARCO, CD36, and macrosialin/CD68. These receptors were clearly demonstrated in the atherosclerotic lesions in double knockout mice as well as LDLR single knockout mice by immunohistochemistry or by reverse transcriptase-polymerase chain reaction. Because the very low density lipoprotein (VLDL) fraction was elevated in the double and single knockout mice, we further examined the possibility that VLDL may participate in foam cell formation in atherosclerotic lesions. When incubated with VLDL isolated from LDLR-deficient mice, cholesterol ester accumulation and foamy transformation occurred in MSR-A-deficient macrophages as well as in normal macrophages. These data indicate that MSR-A plays an essential role in the development of diet-induced atherosclerosis. It also appears that other scavenger receptors, such as MARCO, CD36, and macrosialin/CD68, as well as uptake of VLDL are involved in foam cell formation during atherogenesis in MSR-A/LDLR double knockout mice.

Animals↗
PubMed1998

Immunohistochemical distribution and subcellular localization of three distinct specific molecular structures of advanced glycation end products in human tissues.

Using three mouse anti-human monoclonal antibodies for advanced glycation end products (AGEs), 6D12, 1F6, and 2A2, we examined the immunohistochemical distribution and localization of AGEs in various organs and tissues obtained from nondiabetic autopsy or biopsy cases (men and women, 41 to 86 years of age). 6D12 recognizes Nepsilon-(carboxymethyl)lysine (CML), a nonfluorescent and non-cross-linked AGE structure, and 1F6 recognizes fluorolink, a fluorescent and cross-linked AGE structure. The epitope of 2A2 is unknown but is different from that of CML and fluorolink or other known AGE structures such as pyrraline, pentosidine, and crosslines. Immunohistochemistry with these monoclonal antibodies revealed the intra- and extracellular accumulation of AGEs in these organs and tissues. By double immunohistochemical staining with two of the three monoclonal antibodies in different combinations, positive reaction products for all three monoclonal antibodies were demonstrated in macrophages widely distributed in various organs and tissues; endothelial cells of endocardium, arteries, veins, and blood capillaries; mesenchymal cells; epithelial or parenchymal cells; blood cells; and extracellular matrix. This result indicates that these three different AGE-specific molecules are formed intracellularly and extracellularly. In some cell types, however, one or two of these specific molecules were not always found together, suggesting that the molecular structures of AGEs and their formation are heterogeneous. Immunoelectron microscopy demonstrated the localization of AGE-labeled immunogold particles in the nuclei, nuclear envelope, mitochondria, endoplasmic reticula, Golgi complexes, endocytic vesicles, lysosomal vacuoles or granules, secretory granules, cytosol, and cell membranes, as well as in the extracellular matrix. In addition, the double histochemical staining method for ceroid/lipofuscin and immunohistochemistry for AGEs demonstrated intralysosomal formation and accumulation of AGEs in ceroid/lipofuscin pigments. These results suggest that the extracellularly produced AGEs are taken up by receptors into the cells and accumulate in secondary lysosomes and that AGEs are formed intranuclearly and/or intracellularly, probably via different metabolic pathways.

Adult↗
PubMed1997

A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes.

By searching the expressed sequence tag (EST) database, we identified partial cDNA sequences encoding a polypeptide with significant sequence identity to the human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78 alpha. We determined the complete cDNA sequence that contained a reading frame of 89 amino acids with 61% identity to human MIP-1 alpha/LD78 alpha. The mRNA was expressed constitutively at high levels in human lung and at low levels in some lymphoid tissues. Furthermore, the mRNA was strongly induced in several human cell lines, including monocytic U937 cells, by PMA. From these results, we designated this novel CC chemokine as PARC from pulmonary and activation-regulated chemokine. In situ hybridization analyses showed that alveolar macrophages, follicular dendritic cells in the germinal centers of regional lymph nodes, and peripheral blood monocytes stimulated with LPS express PARC mRNA. Using the human CC chemokine yeast artificial chromosome contig that we constructed recently, we mapped the PARC gene (SCYA18) within one of the two subregions of the CC chemokine gene cluster at chromosome 17q11.2. To investigate its biologic activity, the PARC protein was expressed in insect cells. PARC was chemotactic for both activated (CD3+) T cells and nonactivated (CD14-) lymphocytes, but not for monocytes or granulocytes. Binding analysis using PARC fused with alkaline phosphatase-(His)6 showed the presence of a single class of receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell. Thus, PARC is a novel CC chemokine with a close phylogenic relationship with MIP-1 alpha/LD78 alpha, but with a highly selective activity on lymphocytes.

Amino Acid Sequence↗
PubMed1997

A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Animals↗
PubMed1997

Coinduction of nitric-oxide synthase and arginase I in cultured rat peritoneal macrophages and rat tissues in vivo by lipopolysaccharide.

Nitric oxide is synthesized by nitric-oxide synthase from arginine, a common substrate of arginase. Rat peritoneal macrophages were cultured in the presence of bacterial lipopolysaccharide (LPS), and expression of the inducible isoform of nitric-oxide synthase (iNOS) and liver-type arginase (arginase I) was analyzed. mRNAs for iNOS and arginase I were induced by LPS in a dose-dependent manner. iNOS mRNA appeared 2 h after LPS treatment and increased to a near maximum at 8-12 h. On the other hand, arginase I mRNA that was undetectable prior to the treatment began to increase after 4 h with a lag time and reached a maximum at 12 h. Immunoblot analysis showed that iNOS and arginase I proteins were also induced. mRNA for arginase II, an arginase isozyme, was not detected in the LPS-activated peritoneal cells. mRNA for CCAAT/enhancer-binding protein beta (C/EBPbeta), a transactivator of the arginase I gene, was also induced, and the induction was more rapid than that of arginase I mRNA. Changes in iNOS and arginase I mRNAs were also examined in LPS-injected rats in vivo. iNOS mRNA increased rapidly in the lung and spleen, reached a maximum 2-6 h after the LPS treatment, and decreased thereafter. Arginase I mRNA was induced markedly and more slowly in both tissues, reaching a maximum in 12 h. Thus, arginase I appears to have an important role in down-regulating nitric oxide synthesis in murine macrophages by decreasing the availability of arginine, and the induction of arginase I is mediated by C/EBPbeta.

Animals↗
PubMed1997

The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats.

Collagen-induced arthritis was produced in rats by intradermal immunization with type II collagen and the expression and production of monocyte chemoattractant protein-1 (MCP-1) were examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Northern blot analysis. Two to three weeks after the immunization, the hindfeet showed swelling and redness, followed by the development of severe arthritis, particularly in the ankle joints. During this period, prominent infiltration of neutrophils and macrophages was observed. Sandwich ELISA and Northern blot analysis revealed that MCP-1 concentrations in the joint lavages and MCP-1 mRNA levels in the joint tissues both peaked at 2 weeks after the immunization. By immunohistochemistry, various types of cells, particularly neutrophils, macrophages, synovial cells, and vascular endothelial cells, stained positively for MCP-1. Finally, injection of a neutralizing monoclonal antibody against rat MCP-1 significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30 per cent compared with controls. These results suggest that MCP-1 plays a critical role in this model in the recruitment of monocytes and in the development of arthritis.

Animals↗
PubMed1997

Establishment and characterization of cell lines derived from a transplantable rat malignant meningioma: morphological heterogeneity and production of nerve growth factor.

A cell line (KMY-J) was established from a transplantable tumor (MM-KMY) derived from a spontaneous malignant meningioma arising in an aged F344 rat, and three cloned cell lines (KMY-1, KMY-2 and KMY-3) were induced from the parent KMY-J. Morphologically, KMY-J and tumors induced in syngeneic rats by KMY-J showed cell pleomorphism. All neoplastic cells in KMY-J and its tumors were immunoreactive to vimentin; occasional cells reacted to ED1 (rat macrophage/histiocyte-specific antibody) and alpha-smooth muscle actin (alpha-SMA), indicating expression of histiocytic or myofibroblastic immunophenotypes of meningioma cells. In contrast, KMY-1, KMY-2 and KMY-3 consisted of a uniform cell population differing from each other. KMY-1-induced tumors were similar histologically to meningeal fibrosarcomas. Dendritic cells seen in KMY-2 cultures gave an appearance of arachnoid trabecular cells. In KMY-3 and its tumors, large round cells and multinucleated giant cells were predominant. Cells of these cloned cell lines also reacted to vimentin, but were negative for ED1 and alpha-SMA. By the bioassay using PC12 cells and reverse transcription-polymerase chain reaction for nerve growth factor (NGF) mRNA, production of NGF was demonstrated in the parent and cloned cell lines. The present cell lines may prove useful for studying the histological features of meningeal tumors and the bioactive factors produced by meningeal cells.

Animals↗
PubMed1997

Expression of monocyte chemoattractant protein-1 in experimental crescentic glomerulonephritis in rats.

Crescentic glomerulonephritis (CGN) is a rapidly progressive glomerular disease that is usually associated with a poor prognosis. Monocytes/macrophages are frequently observed in glomeruli in cases of CGN, and they are considered to play a crucial role in the pathogenesis of this disease. In this study we analyzed the glomerular expression of monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, in an experimental model of CGN. A model of the disease was induced in the WKY strain of rats by intravenous injection of antiserum raised against glomerular basement membranes. Accumulation of monocytes/macrophages in glomeruli was observed 4 hours after the injection of antiserum. Northern blot analysis showed that the expression of mRNA for MCP-1 was enhanced within 4 hours, peaked on day 3--when it was 60 times that in the control--and then declined. Immunostaining with MCP-1-specific antibody revealed the expression of MCP-1 protein in the diseased glomeruli but not in control glomeruli. Quantitative analysis of glomerular MCP-1 protein by enzyme-linked immunosorbent assay revealed a level 46 times that in the control in reflecting the increase in mRNA for MCP-1. These results indicate that glomeruli of rats with CGN produce MCP-1, which may play an important role in the pathogenesis of glomerular inflammation and crescent formation in CGN.

Animals↗
PubMed1997

A novel monoclonal antibody, RM-4, specifically recognizes rat macrophages and dendritic cells in formalin-fixed, paraffin-embedded tissues.

An anti-rat macrophage/dendritic cell monoclonal antibody, RM-4, was produced using a homogenate of silica-induced lung granulomas of rat as immunogen. Immunohistochemistry demonstrated that RM-4 was specific for macrophage and dendritic cell populations residing in various organs and tissues. It did not react with any cells other than macrophage/dendritic cells. In the double staining of the spleen, RM-4-positive macrophages showed wider distribution than those of the four other anti-rat macrophage monoclonal antibodies compared. The immunoreactivity of RM-4 was well preserved not only in frozen sections but also in formalin-fixed, paraffin-embedded tissues. The isotype of the monoclonal antibody was IgG1 kappa and its antigen molecular weight was 46 kDa. Immunoelectron microscopy revealed positive reaction products for RM-4 on the membrane of endosomes and lysosomes in macrophages and epidermal Langerhans cells. Reaction intensity increased after thioglycolate elicitation or endocytosis regardless of ingested materials. From these data, it is concluded that RM-4 recognizes a membrane protein of endolysomes in macrophages and dendritic cells. The antigen may play a role in endolysosomal processing. RM-4 is considered to be a useful tool not only for identifying macrophage/dendritic cells both in frozen and paraffin-embedded tissues, but also for evaluating their endolysosomal processing.

Animals↗
PubMed1997

Detailed analysis of phenotypes of macrophages infiltrating glomeruli in rat anti-Thy1 nephritis.

A phenotypic analysis of infiltrating macrophages in rat anti-Thy1 glomerulonephritis induced by monoclonal antibody (mAb) 1-22-3 was carried out using recently reported macrophage-specific mAbs. This was combined with a more detailed quantitative analysis, counting positive cells in isolated glomeruli, to obtain more information on the roles played by macrophages in glomerulonephritis. In normal glomeruli a small number of ED1- or OX-3(anti-Ia)-positive cells but almost no ED2-, TRPM-3- or Mar-3-positive cells were observed. ED1-positive cells increased from 2 h and peaked between days 3 and 7 after mAb injection. TRPM-3-positive cells increased from day 3 and peaked on day 7, later than ED1. The numbers of OX-3-positive cells changed in parallel with those of ED1-positive cells. Mar-3, which stained blood monocytes and ED2, which is an indicator oftissue-fixed resident macrophages, did not react with glomerular infiltrating macrophages. In a double staining study, about 40% of ED1- or OX-3-positive cells costained with TRPM-3 on day 3 and the percentage increased on day 7, but hardly any cells were positive for TRPM-3 alone. This results in two different phenotypes (ED1+,ED2-,OX-3+,Mar-3-, TRPM-3- and ED1+,ED2-,OX-3+,Mar-3-,TRPM-3+) of infiltrating macrophages. We conclude that in rat anti-Thy1 glomerulonephritis, monocytes/macrophages may infiltrate the mesangium, rapidly changing their phenotype (Mar-3+ to Mar-3-) and resulting in a gradual shift to TRPM-3-positive, activated macrophages.

Animals↗
PubMed1997

Tissue factor expression on macrophages in coronary plaques in patients with unstable angina.

Tissue factor is a membrane-bound glycoprotein that functions in the extrinsic pathway of blood coagulation by acting as a cofactor for factor VII, and the resulting complex leads to thrombin production in vivo. The purpose of the present study is to determine whether macrophages express tissue factor in human coronary atherosclerotic plaques. We examined directional coronary atherectomy specimens from 24 patients with unstable angina and 23 with stable exertional angina. In these specimens, macrophages were detected in 22 (92%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .003). The percentage of macrophage infiltration area was significantly larger in patients with unstable angina than in those with stable exertional angina (17 +/- 3% versus 6 +/- 2%, P = .008). The immunohistochemical double staining revealed the expression of tissue factor on macrophages in 18 (75%) of 24 patients with unstable angina versus 3 (13%) of 23 with stable exertional angina (P < .0001). Thrombus was identified in 20 (83%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .02). Fibrin deposition was mainly observed around macrophages expressing tissue factor in the patients with unstable angina. We have shown that tissue factor expression on macrophages was more frequent in coronary atherosclerotic plaques in patients with unstable angina. Tissue factor expressed on macrophages may play an important role in the thrombogenicity in coronary atherosclerotic plaques of these patients.

Aged↗
PubMed1997

Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats.

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.

Animals↗