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J M Wang

Publications and source records attributed to J M Wang.

At least 127 records · Page 7Linked to original sources
PubMed1997

Differential expression of binding sites for chemokine RANTES on human T lymphocytes.

The C-C chemokine RANTES, a T lymphocyte chemoattractant, is considered an important mediator of inflammation, allergy, and host defense against HIV-1 infection. In this study, we investigated the modulation of binding of RANTES to T lymphocytes. Human peripheral blood CD3+ T cells, when freshly isolated from buffy-coat blood, expressed a considerable number of high-affinity binding sites for RANTES. These cells also showed significant chemotactic migration in response to RANTES in vitro. After 6-15 h incubation at 37 degrees C, the binding of RANTES, but not of macrophage inflammatory protein-1 alpha (MIP-1 alpha) or of monocyte chemotactic protein-3 (MCP-3), consistently increased. Scatchard analyses indicated that the number of binding sites for RANTES increased about threefold by 15 h without any change in the affinity. The increase in RANTES binding was no longer detected by 24 h. This increase in the specific binding was mainly attributable to CD4+ T cells and was not associated with increased chemotactic activity of these cells in response to RANTES. Incubation with anti-CD3 antibody for 15 h markedly reduced the binding capability of T cells for RANTES and was associated with decreased chemotactic activity. On the other hand, when T cells were incubated with interleukin-2 (IL-2) for 1 week, the specific binding for all three C-C chemokines, RANTES, MIP-1 alpha, and MCP-3 was markedly increased in comparison to cells cultured in the absence of IL-2. These results suggest that the expression of binding sites on T cells for RANTES is differentially modulated, indicating the existence of novel receptors for RANTES that do not bind MIP-1 alpha.

Antibodies, Monoclonal↗
PubMed1997

Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage.

Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP-2 was originally identified by amino acid sequence analysis as a CXC chemokine co-produced with IL-8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP-2 was disclosed by means of RT-PCR. Similarly, mouse GCP-2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP-2 share 61% identical amino acids. Both chemokines occur as multiple NH2-terminally truncated forms. The shorter forms of mouse, but not those of human, GCP-2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP-2 was a more potent neutrophil activator than human GCP-2, natural mouse KC, and MIP-2. Human GCP-2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP-2 induction by IL-1beta. Human GCP-2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL-8, GROalpha, and ENA-78. Human GCP-2 induced [Ca2+]i increases and chemotactic responses in both CXCR1- and CXCR2-transfected cells. Finally, GCP-2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP-2 complements the activity of IL-8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP-2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP-2-secreting tumor cells.

Amino Acid Sequence↗
PubMed1997

Regulation of CCR2 chemokine receptor mRNA stability.

During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. Cytokine messages containing A-U-rich elements located in the 3' untranslated region (ARE) are the best studied examples of this process. AREs have been shown to act as targeting motifs for degradation of cytokine and transcription factor messages. We have recently observed that the interleukin-8 (IL-8) receptor messages, IL-8RA and B (CXCR1 and CXCR2), also undergo changes in stability in response to the inflammatory stimulator lipopolysaccharide (LPS). To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR2 (monocyte chemotactic protein-1 receptor) is also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CCR2 message through message degradation. Furthermore, LPS stimulated the decay of Poly(A) CCR2 mRNA faster than total CCR2 RNA, indicating that deadenylation is the first step in LPS-induced CCR2 RNA degradation. We conclude from these experiments that LPS stimulates the rapid degradation of CCR2 messages through a two-step process, deadenylation followed by degradation of the message body. In contrast to the results obtained for CCR2 mRNA, macrophage inflammatory protein-1alpha messages, which contain an ARE motif, were stabilized by LPS stimulation, indicating that chemokine and chemokine receptor mRNA stability are regulated by different and opposing mechanisms.

Adenine↗
PubMed1997

IL-8 and NAP-2 differ in their capacities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B.

Two receptors for interleukin 8 (IL-8), IL-8rA and IL-8rB, have been cloned. Previous studies of neutrophils indicated that the two C-X-C chemokines, IL-8 and NAP-2, bind to IL-8rB with high affinity but that only IL-8 binds to IL-8rA with high affinity. In this study, human kidney embryonal 293 cells were transfected to express solely IL-8rA or IL-8rB (the cells are designated IL-8rA/293 and IL-8rB/293, respectively). The authors show that NAP-2 bound both IL-8rA and IL-9rB specifically. While NAP-2 and IL-8 bound IL-8rB with comparable high affinity (2.9 +/- 0.5 and 2.8 +/- 0.8 nM, respectively), NAP-2 showed a lower binding affinity to IL-8rA (9 +/- 2 nM) compared with IL-8 (1.3 +/- 0.5 nM). A lower number of binding sites was detected for NAP-2 than for IL-8 on IL-8rA/293 cells as well on IL-8rB/293 cells. On both cell types (IL-8rA/293 and IL-8rb/293), NAP-2 and IL-8 could completely inhibit [125I]NAP-2 binding, while unlabelled NAP-2 could only partially compete for [125I]IL-8 binding. Functional assays revealed that although NAP-2 is chemotactic for both IL-8rA/293 and IL-8rB/293 cells, it is less potent than IL-8. While NAP-2 induced chemotaxis of IL-8rB/293 cells at the same optimal concentrations as IL-8 (10-100 ng/ml), the induction of optimal migratory response of IL-8rA/293 cells required much higher concentrations of NAP-2 than IL-8 (1000-3000 ng/ml and 10-100 ng/ml, respectively). The dose-response curve of the IL-8rB/293 cells to IL-8 was bell shaped, while the response to NAP-2 was sustained at a plateau level even at concentrations as high as 3000 ng/ml. It is likely that tertiary structural differences between NAP-2 and IL-8 account for their divergent abilities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B.

Antigens, CD↗
PubMed1997

Genetic isolation of a chromosome 1 region affecting blood pressure in the spontaneously hypertensive rat.

Recent linkage studies in the spontaneously hypertensive rat (SHR) suggest that a blood pressure regulatory gene or genes may be located on rat chromosome 1q. To investigate this possibility, we replaced a region of chromosome 1 in the SHR (defined by the markers D1Mit3 and Igf2) with the corresponding chromosome segment from the normotensive Brown-Norway (BN) strain. In male SHR congenic rats carrying the transferred BN chromosome segment, 24-hour average systolic and diastolic blood pressures were significantly lower than in male progenitor SHR. Polymerase chain reaction genotyping using 60 polymorphic microsatellite markers dispersed throughout the genome confirmed the congenic status of the new strain designated SHR.BN-D1Mit3/Igf2. These findings provide direct evidence that a blood pressure regulatory gene exists on the differential segment of chromosome 1 that is sufficient to decrease blood pressure in the SHR. The SHR.BN-D1Mit3/Igf2 congenic strain represents an important new model for fine mapping and characterization of genes on chromosome 1 involved in the pathogenesis of spontaneous hypertension.

Animals↗
PubMed1997

Prospects for cytokine and chemokine biotherapy.

Cytokines with immunostimulating effects have the capacity to induce tumor immunity in animal models, whereas some cytokines interfere with tumor growth based on their angiostatic effects. Despite these capabilities, cytokines, such as IFN-, IFN-, tumor necrosis factor, interleukin (IL)-1, and IL-2, have had limited clinical efficacy and many undesirable side effects. In preclinical models, cytokines can even promote tumor growth and increase metastatic spread. Although chemokines have had limited clinical evaluation, studies of animal models show that they can also have tumor-suppressive or tumor-enhancing effects. In mice, chemokines, such as IP-10, RANTES, and TCA3, have resulted in tumor regression and immunity to subsequent tumor challenge. Those chemokines that are angiostatic (e.g., PF4, IP-10, and MIG) can also induce tumor regression by reducing the tumor blood supply. Conversely, IL-8, which is angiogenic, can promote tumor growth. Our studies show that nasopharyngeal cell line cells (FADU) show a chemotactic as well as a proliferative response to MCP-1. In addition, a variant murine T cell lymphoma cell line Esb-MP, unlike the parental variant Esb, was selectively chemoattracted by murine MCP-1/JE. When injected s.c. into mice, the Esb-MP variant metastasized to the kidney with much higher frequency than the Esb variant. Both cultured kidneys from normal mice and a mesangial cell line constitutively produced chemoattractants that acted on Esb-MP but not Esb parental cells. Purification to homogeneity of these chemoattractants led to the identification of RANTES and JE. These results demonstrate that some chemokines may promote tumor growth and organ-specific metastatic spread of those tumors that have adapted and become responsive to chemokines. Finally, tumors appear to use numerous adaptive mechanisms to subvert and suppress the immune system. More effective therapy with cytokines and chemokines will require better characterization of the means by which tumors develop resistance to cytokines and overcome the immune system. Only then can we develop appropriate therapeutic approaches to antagonize cancer-induced immunosuppression.

Animals↗
PubMed1996

Expression of angiotensinogen mRNA and localization of angiotensin II and renin in peripheral adrenergic neurons in primary culture.

Although the presence of a local renin-angiotensin system has been established in a number of tissues, evidence for the existence and expression of the components of the renin-angiotensin system in peripheral adrenergic neurons is still missing. Here we provide the results showing the expression of angiotensinogen mRNA and localization of renin and angiotensin II in primary cultured fetal pig superior cervical ganglion neurons but not in non-neuronal cells by in situ hybridization with biotinylated oligodeoxynucleotide probe and immunocytochemical approaches. Our confocal laser scanning microscopical results confirm that angiotensinogen mRNA is expressed in the renin containing neurons. These results, for the first time, provide direct evidence that peripheral adrenergic neurons are not only target cells of angiotensin, but are also a local angiotensin generating source.

Adrenergic Fibers↗
PubMed1996

Construction of human factor IX expression vectors in retroviral vector frames optimized for muscle cells.

Development of a highly refined human factor IX (hFIX) expression vector system is critical for establishing a durable hemophilia B gene therapy. Here we report construction of a series of retroviral vectors and identification of an optimal basic structure and components for expressing hFIX in skeletal muscle cells. These vectors, which are derived from Moloney murine leukemia virus (MoMLV) with its enhancer sequence in the 3' long terminal repeat (LTR) deleted, contained internal hFIX expression units inserted in forward configuration without or with a viral vector intron sequence (pdL or pdLIn vector frame, respectively) or in inverted configuration without a viral vector intron sequence (pdLi frame). Internal expression units contained a hFIX cDNA or hFIX minigene (hIXm1 or hIXm2) derived from the hFIX cDNA by insertion of a shortened first intron sequence of the hFIX gene. Regardless of the promoter and vector frame used, both hIXm1 and hIXm2 gave 10- to 14-fold higher hFIX expression compared to those with hFIX cDNA. Internal hFIX transcriptional control units of these vectors were composed of various promoters linked with or without the muscle creatine kinase enhancer (Me) sequence. Promoters tested included those of alpha-actin (alpha A775), beta-actin (beta A280), cytochrome oxidase (CO1250 and CO650), myogenin (Mg1031 and Mg353), and Rous sarcoma virus (RSV). beta A200, which was derived from beta A280 by eliminating potential polyadenylation sites, was also tested. As extensively examined with the myogenin promoter, presence of one or multiple copies of Me in the vectors elevated the expression activity in myotubes by 4.5- to 19-fold over those without Me, but not significantly in myoblasts. Similar enhancements in expression activity with Me were also observed with other promoters, except those of RSV and CO. The latter two showed only modest enhancements in the presence of Me. As assayed with myotubes in culture, the general order of hFIX expression activity of various promoters with four copies of Me in the three different vector frames was beta A280 approximately beta A200 > Mg353 > Mg1031 approximately RSV approximately CO650 approximately alpha A775 > CO1250. One exception was that CO650 showed significantly less activity in pdLi-type vectors than in the pdLIn vectors. Based on the systematic analyses of various structural components, a group of pdLi vectors consisting of beta A200, two to four copies of Me, and hIXm2 was identified to have the optimal basic vector structure to be used in retrovirus for hFIX expression in differentiated skeletal muscle cells. The present studies provide the critical first step for establishing a highly refined hemophilia B gene therapy based on skeletal muscle-targeted hFIX gene transfer.

Animals↗
PubMed1996

Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat.

The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the spontaneously hypertensive rat and normotensive Brown-Norway (BN.Lx) rat fed normal and high cholesterol diets. QTLs regulating lipid phenotypes were mapped by scanning the genome with 534 genetic markers. A significant relationship (P < 0.00006) was found between basal HDL2 cholesterol levels and the D19Mit2 marker on chromosome 19. Analysis of congenic strains of spontaneously hypertensive rat indicated that QTLs regulating postdietary lipid phenotypes exist also on chromosomes 8 and 20. Previous studies in the recombinant inbred and congenic strains have demonstrated the presence of blood pressure regulatory genes in corresponding segments of chromosomes 8, 19, and 20. These findings provide support for the hypothesis that blood pressure and certain lipid subfractions can be modulated by linked genes or perhaps even the same genes.

Animals↗
PubMed1996

Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils.

Reports that interleukin-8 (IL-8) induces the infiltration of neutrophils followed by T-cells into injection sites led us to postulate that by stimulation of neutrophil degranulation IL-8 may cause the release of factors with chemoattractant activity for T-lymphocytes. Extracts of human neutrophil granules were chromatographed to isolate and purify T-lymphocyte chemoattractant factors. Two major peaks of T-cell chemotactic activity were purified by C18 reversed phase high pressure liquid chromatography (HPLC). The first peak was resolved further by C4 reversed phase HPLC and yielded an active fraction shown by NH2-terminal amino acid sequence analysis to contain defensins HNP-1, HNP-2, and HNP-3. Purified defensins HNP-1 and HNP-2 (kindly provided by Dr. R. I. Lehrer, UCLA) were also potent chemoattractants for human T-cells, while HNP-3 was inactive. The second peak of T-cell chemoattractant activity was also further purified to homogeneity by C4 reversed phase HPLC and identified by NH2-terminal sequence analysis as CAP37/azurocidin, a protein with sequence homology to serine proteases. 0.1 100 ng of defensins and 1.0 100 ng/ml CAP37 were able to stimulate in vitro T-cell chemotaxis. Neutrophil activating factors, i.e. IL-8, phorbol 12-myristate 13-acetate/ionomycin, and formylmethionylleucylphenylalanine each induced the release of CAP37 and defensins from neutrophil granules. Subcutaneous administration of defensins or CAP37/azurocidin into BALB/c mice resulted in a moderate neutrophil and mononuclear cell infiltrate by 4 h, which was greater by 24 h at the site of injection. Additionally, subcutaneous injection of defensins into chimeric huPBL-SCID mice resulted in significant infiltration by human CD3+ cells within 4 h. These results identify the antimicrobial proteins, CAP37/azurocidin and defensins HNP-1 and HNP-2, as potent neutrophil-derived chemoattractants for T-cells. These proteins represent primordial antimicrobial peptides which may have evolved into acute inflammatory cell-derived signals that mobilize immunocompetent T-cells and other inflammatory cells.

Amino Acid Sequence↗
PubMed1996

Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.

Alleles↗
PubMed1996

Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro.

Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34+ progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a+ DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP1 alpha), MIP-1 beta, and RANTES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a+ cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14+ monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense.

Binding Sites↗
PubMed1996

A genetic linkage map of the rat derived from recombinant inbred strains.

We have constructed a genetic linkage map in the rat by analyzing the strain distribution patterns of 500 genetic markers in a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown-Norway rat (HXB and BXH recombinant inbred strains). 454 of the markers could be assigned to specific chromosomes, and the amount of genome covered by the mapped markers was estimated to be 1151 centimorgans. By including a variety of morphologic, biochemical, immunogenetic, and molecular markers, the current map integrates and extends existing linkage data and should facilitate rat gene mapping and genetic studies of hypertension and other complex phenotypes of interest in the HXB and BXH recombinant inbred strains.

Animals↗
PubMed1996

Serum levels of the TGF-beta receptor are increased in atherosclerosis.

Murine monoclonal antibody E9 recognises a transforming growth factor (TGF) beta receptor, which is expressed in increased amounts by activated endothelial cells. In order to examine the biological role of this molecule in atherosclerosis, we have measured levels of the TGF-beta receptor alongside those of two other endothelial cell products (von Willebrand factor and soluble E-selectin) in the serum of 55 patients with atherosclerosis (29 with ischaemic heart disease and 26 with peripheral vascular disease), and in a cohort of 26 age- and sex-matched asymptomatic controls. There were increased levels of the TGF-beta receptor (P = 0.0079) and von Willebrand factor (P = 0.0001), but not soluble E-selection in patients' serum relative to the controls. In multivariate analysis of the endothelial cell products against total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, age, sex and smoking, both the TGF-beta receptor and von Willebrand factor correlated with total cholesterol (Spearman's r = 0.37 and r = 0.35, respectively, both P < 0.001). Lack of a correlation with a coarse endothelial damage marker von Willebrand factor or soluble E-selectin (produced by immunologically stimulated endothelial cells) implies other mechanisms are responsible for increased levels of the TGF-beta receptor in serum of patients with atherosclerosis.

Aged↗
PubMed1996

Dexamethasone and cyclosporin A modulation of cytokine expression and specific antibody synthesis in an allergic bronchopulmonary aspergillosis murine model.

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanced and dexamethasone inhibited the Aspergillus fumigatus-induced pulmonary eosinophilia and total IgE levels. To evaluate whether these effects were related to the modulation of T-lymphocyte recruitment and activation and cytokine expression, we performed immunohistochemical staining for T-cell surface marker CD3 and CD4, cell activation marker CD25, and cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sections from mice exposed to Aspergillus fumigatus and treated or not with dexamethasone or cyclosporin A. Dexamethasone significantly inhibited Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonary eosinophils. In contrast, cyclosporin A did not decrease these immunological events but enhanced the lung eosinophil recruitment. Moreover, dexamethasone prevented the production of immunoglobulins against 76 and 36 kD antigen proteins and cyclosporin A against 76 and 18 kD antigen proteins. These results indicate that dexamethasone down-regulates and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activation and GM-CSF, IL-4 and IL-5 expression. Both drugs inhibit Aspergillus fumigatus-specific antibody synthesis, but their suppressive actions are selective to different antigenic components.

Animals↗
PubMed1996

Immunohistochemical detection of GM-CSF, IL-4 and IL-5 in a murine model of allergic bronchopulmonary aspergillosis.

BACKGROUND: Granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and IL-5 are important in tissue eosinophil accumulation and high IgE production in allergic inflammatory reaction. OBJECTIVE: We examine lung GM-CSF, IL-4 and IL-5 expression in a murine model of allergic bronchopulmonary aspergillosis (ABPA) characterized by eosinophil and lymphocyte lung infiltration and elevated serum IgE level. METHODS: C57BL/6 mice were intranasally treated three times a week for 1, 2 or 3 week(s) with Aspergillus fumigatus (Af) antigen or saline and were sacrificed on days 7, 14 and 21. Immunohistochemical analyses for GM-CSF, IL-4 and IL-5 were performed on lung sections. RESULTS: Af treatment induced a remarkable pulmonary eosinophil influx. Increased numbers of lung T lymphocytes and GM-CSF positive cells were observed on days 14 and 21. IL-4 and IL-5 positive cells were increased significantly only on day 14. Immunostained serial sections showed that most (> or = 98%) cytokine positive cells were CD3 positive. Few eosinophils (< 2% of cytokine positive cells) were immunoreactive for GM-CSF and IL-5. Significant correlations were found between the number of GM-CSF and IL-5 positive cells, and the number of eosinophils in Af-treated lung (r = 0.62, P < 0.05 and r = 0.52, P < 0.05 respectively), and between the number of IL-4 positive cells and the serum total IgE level (r = 0.64, P < 0.01). CONCLUSIONS: Our data suggest a role for T lymphocyte GM-CSF, IL-4 and IL-5 in Af-induced mouse pulmonary eosinophilia and increased serum IgE production and further support the importance of T helper (TH2) cells in the pathogenesis of ABPA.

Animals↗