Biomedical subjects

Cord Sunderkötter

Publications and source records attributed to Cord Sunderkötter.

At least 19 recordsLinked to original sources

PubMed2006

MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program.

Activated phagocytes express considerable amounts of MRP8 and MRP14, 2 calcium-binding S100 proteins forming stable heterodimers that are specifically secreted at inflammatory sites in many diseases. We previously reported that treatment of human microvascular endothelial cells with purified MRP8/MRP14 leads to loss of endothelial cell contacts. In this study, we demonstrate that MRP8/MRP14 complexes furthermore trigger cell death of endothelial cells after the onset of cell detachment. Morphologic analysis of dying endothelial cells revealed characteristic features of both apoptosis and necrosis. Furthermore, MRP8/MRP14 induced apoptotic caspase-9 and caspase-3 activation, DNA fragmentation, and membrane phosphatidylserine exposure in target cells. These events were independent of death receptor signaling and in part controlled by a mitochondrial pathway. Consistently, overexpression of antiapoptotic Bcl-2 abrogated caspase activation and externalization of phosphatidylserine; however, MRP8/MRP14 still induced plasma membrane damage and even DNA fragmentation. Thus, our results demonstrate that MRP8/MRP14 triggers cell death via caspase-dependent as well as -independent mechanisms. Excessive release of cytotoxic MRP8/MRP14 by activated phagocytes might therefore present an important molecular pathomechanism contributing to endothelial damage during vasculitis and other inflammatory diseases.

Apoptosis↗

PubMed2006

Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes.

Monocytes and macrophages may either promote or down-regulate inflammatory reactions depending on their state of activation. The effects of glucocorticoids (GCs), the most widely used immunosuppressive drugs, on monocytes are currently not well defined. By analyzing the GC-induced expression pattern in human monocytes by microarray technology, we identified for the first time GC-dependent regulation of 133 genes, including anti-inflammatory molecules such as adenosine A3 receptor, CD1d, and IL-1 receptor II. The results were independently confirmed by real-time polymerase chain reaction (PCR) and flow cytometry. Functional clustering of GC-regulated genes indicated induction of monocytic properties such as phagocytosis and motility as well as repression of adhesion, apoptosis, and oxidative burst. These predictions were confirmed by independent functional assays. GCs up-regulate fMLP receptors and specifically promote chemotaxis to this chemoattractant. Furthermore, GCs promote survival of an anti-inflammatory monocytic phenotype in inflammatory reactions, probably by inhibition of apoptosis because of oxidative stress. GCs limit tissue damage because of induction of antioxidative properties and high capacity for phagocytosis of proinflammatory agents. Thus, GC treatment did not cause a global suppression of monocytic effector functions but results in differentiation of a specific anti-inflammatory phenotype which seems to be actively involved in resolution of inflammatory reactions.

Apoptosis↗

PubMed2006

[Antimicrobial therapy in dermatology].

The extensive and sometimes indiscriminate use of antibiotics sometimes without strict indications has led to increases in both bacterial resistance and sensitization of patients. Systemic antibiotics in skin infections are indicated when a severe local infection occurs which spreads into the surrounding tissue or when there are signs of systemic infection. There are special indications in patients with peripheral arterial occlusive disease,diabetes or immunosuppression. Topical use of antibiotics should be abandoned and replaced by antiseptics. The beta-lactam antibiotics are the antibiotics of first choice for many skin infections. They are usually effective, have a well-defined profile of adverse events and most are affordable. Penicillin G or V are the first line treatment for erysipelas. Infections with Staphylococcus aureus are usually treated with isoxazolyl penicillins or second generation cephalosporins. In mixed infections in patients with diabetes or peripheral arterial occlusive disease,the treatment of choice is metronidazole plus beta-lactam-/beta-lactamase inhibitor antibiotics, but quinolones or second generation cephalosporins can also be used, once again with metronidazole. The aim of this review is to define the indications for antibiotics in dermatology, to highlight their modes of action and adverse effects and to make suggestions for rational antibiotic therapy in cutaneous infections frequently encountered in the practice of dermatology.

Administration, Topical↗

PubMed2006

[Post-marketing surveillance on treatment of 5,665 patients with atopic dermatitis using the calcineurin inhibitor pimecrolimus: positive effects on major symptoms of atopic dermatitis and on quality of life].

BACKGROUND: Topical application of the calcineurin inhibitors pimecrolimus and tacrolimus is a current major advance in the therapy of atopic dermatitis. The aims of this post-marketing surveillance were: a) to acquire data on the efficacy and tolerability of pimecrolimus ointment (Elidel) on a very large cohort of patients from outpatient clinics, and b) to assess changes in their quality of life, a parameter not often considered in previous studies. PATIENTS AND METHODS: Included were 5,665 patients with atopic dermatitis. During the observation period, data on efficacy and tolerability were obtained at the beginning of the study, 3 to 10 days after initiation of therapy and after 4 to 6 weeks. Evaluation of symptoms as well as assessment of efficacy and tolerability were based on linear scales and on the percentage of the body surface area (% BSA) involved. Quality of life was assessed by the German version of the "Dermatology Life Quality Index (DLQI)" or the "Children's Dermatology Life Quality Index (CDLQI)". RESULTS: In this largest post-marketing surveillance hitherto performed in Germany, the efficacy of pimecrolimus was judged as "good" by 79.3 % of physicians and by 76.5 % of patients. Tolerability was assessed as "good" by 87.2 % of physicians and by 83.1 % of patients. Major symptoms of atopic dermatitis such as pruritus, erythema or lichenification showed marked reduction after just 3 to 10 days, signalling general improvement of the skin disease. In addition, application of pimecrolimus resulted in a significant improvement of the quality of life scores in both children and adults. CONCLUSION: The present study demonstrates that the good efficacy and tolerability of pimecrolimus ointment which had been shown in controlled trials: i) could also be demonstrated on a very large cohort of patients with atopic dermatitis when used in the outpatient setting, and ii) were paralleled by a significant improvement in the quality of life.

Adolescent↗

PubMed2006

Treatment of scabies with 5% permethrin cream: results of a German multicenter study.

BACKGROUND: Until recently, no prescription drug containing permethrin for the therapy of scabies was available on the German market.Therefore, a 5% permethrin cream formulation (InfectoScab 5%) was tested in a single-arm multi-center study including adults and children from 3 months of age with proven scabies. PATIENTS AND METHODS: On day 0, patients were treated once with permethrin cream in the study center. Control examinations including dermatoscopy were performed on day 14+/-2 and on day 28+/-3. Patients who were not considered cured or who had contact to individuals with untreated scabies received one further treatment with permethrin cream on day 14+/-2. Itching and local tolerability of the cream were documented in patients' diaries. Side effects were assessed by history, skin inspection and evaluation of patients' notes. RESULTS: 106 patients in 13 centers were enrolled in the study. Their mean age was 29.2 years (range, 141 days to 71.9 years); 34% of them were children or adolescents. 78.3% of patients were either severely (3 body sites) or very severely (4-5 sites) affected. The cure rate on day 28+/-3 was 95.1% (95% confidence interval, 91.0-99.3%). Pruritus declined markedly and continuously. In general, the cream was well tolerated; side effects were almost invariably mild. CONCLUSIONS: Our results support the efficacy and safety of 5% permethrin cream in adults, children and infants suffering from scabies. These results have contributed to the approval of InfectoScab 5% in Germany for the treatment of scabies in October 2004.

Administration, Topical↗

PubMed2006

Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation.

The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of beta2 integrins (CD11/CD18) to only 2-16% of WT levels. Previously we found that this chronic psoriasiform skin inflammation also depends on the presence of CD4+ T cells. Herein we investigated the role of macrophages in this CD18hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice and were identified as being an important source of TNF-alpha in vivo. Both depletion of macrophages and neutralization of TNF-alpha resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-alpha into the skin of healthy CD18hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but neither substance alone, resulted in the induction of psoriasiform skin inflammation around the injection sites with recruitment and activation of macrophages. Collectively, our data suggest that maintenance of psoriasiform skin inflammation critically depends on efficient recruitment and activation of macrophages with sufficient release of TNF-alpha.

Animals↗

PubMed2005

Wound-healing defect of CD18(-/-) mice due to a decrease in TGF-beta1 and myofibroblast differentiation.

We studied the mechanisms underlying the severely impaired wound healing associated with human leukocyte-adhesion deficiency syndrome-1 (LAD1) using a murine disease model. In CD18(-/-) mice, healing of full-thickness wounds was severely delayed during granulation-tissue contraction, a phase where myofibroblasts play a major role. Interestingly, expression levels of myofibroblast markers alpha-smooth muscle actin and ED-A fibronectin were substantially reduced in wounds of CD18(-/-) mice, suggesting an impaired myofibroblast differentiation. TGF-beta signalling was clearly involved since TGF-beta1 and TGF-beta receptor type-II protein levels were decreased, while TGF-beta(1) injections into wound margins fully re-established wound closure. Since, in CD18(-/-) mice, defective migration leads to a severe reduction of neutrophils in wounds, infiltrating macrophages might not phagocytose apoptotic CD18(-/-) neutrophils. Macrophages would thus be lacking their main stimulus to secrete TGF-beta1. Indeed, in neutrophil-macrophage cocultures, lack of CD18 on either cell type leads to dramatically reduced TGF-beta1 release by macrophages due to defective adhesion to, and subsequent impaired phagocytic clearance of, neutrophils. Our data demonstrates that the paracrine secretion of growth factors is essential for cellular differentiation in wound healing.

Actins↗

PubMed2005

Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion.

Toll-like receptor (TLR) ligands lead to the induction of proinflammatory cytokines and are potent enhancers of specific immune responses. We show here that a single systemic dose of R-848, a ligand for TLR7, potently enhanced hapten sensitization during the induction of contact hypersensitivity (CHS). However, R-848 administration also resulted in a rapid and almost complete depletion of leukocytes from the blood. This effect was transient and was associated with general induction of endothelial adhesiveness. In response to R-848, endothelial cells up-regulated adhesion molecules in vitro and in vivo and leukocytes exhibited increased rolling on endothelia in R-848-treated animals. Adhesion molecule induction appeared to be a direct effect, because endothelial cells expressed TLR7 in vitro and in vivo. After R-848 treatment, the tissue residence time of leukocytes was markedly prolonged in all major peripheral organs. The resulting transiently reduced availability of peripheral-blood leukocytes (PBLs) (TRAP) significantly inhibited otherwise potent CHS responses until the effector cells returned. Thus, although TLR7 ligands are effective adjuvants for the induction of cell-mediated immunity, they can transiently inhibit the elicitation of localized immune responses, possibly due to a systemic endothelial activation throughout the vasculature.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Decorin, a novel player in the insulin-like growth factor system.

Decorin is a multifunctional proteoglycan that is expressed by sprouting endothelial cells. Its expression supports capillary formation and cell survival. Previously, it was shown that some effects of decorin are mediated by protein kinase B and the cyclin-dependent kinase inhibitor, p21. However, the cell surface receptor responsible for these effects was unknown. We demonstrate that decorin binds to the insulin-like growth factor-I (IGF-I) receptor on endothelial cells with an affinity in the nanomolar range (K(D) = 18 nm), which is comparable with IGF-I (K(D) = 1.2 nm). Furthermore, decorin can bind IGF-I itself, but with a lower affinity (K(D) = 190 nm) than classical IGF-I-binding proteins. Decorin addition causes IGF-I receptor phosphorylation and activation, which is followed by receptor down-regulation. These effects are caused by the core protein of decorin, and the binding region could be mapped to the N terminus of the molecule. The physiological relevance of the decorin/IGF-I receptor interaction was corroborated in two animal models (e.g. inflammatory angiogenesis in the cornea and unilateral ureteral obstruction). In both models the IGF-I receptor was up-regulated in decorin-deficient mice compared with controls and the up-regulation could not compensate the decorin deficiency in the disease models. These data indicate that decorin is an important player in the IGF system and its loss cannot fully be compensated in different types of diseases.

Animals↗

PubMed2005

Early activation of cutaneous vessels and epithelial cells is characteristic of acute systemic onset juvenile idiopathic arthritis.

In biopsies of 16 patients (mean: 5.2 years) with acute systemic onset juvenile idiopathic arthritis (SOJIA), we analysed the initial cellular events during the characteristic cutaneous rash for composition of the infiltrate and for expression of activation markers on epithelial and endothelial cells. Despite the fleeting nature of the rash, there was a characteristic infiltration of neutrophils and monocytes, accompanied by a marked expression of endothelial adhesion receptors. In addition, we found a general activation of the cutaneous epithelium reflected by the expression of the pro-inflammatory S100-proteins - myeloid-related protein 8 (MRP8) and MRP14. In responders to therapy, follow-up biopsies showed a complete normalization of these inflammatory parameters, whereas non-responders presented with continuous signs of activation. In conjunction with the high level of epithelial activation, we detected an infiltrate of leucocytes within epithelium of sweat gland ducts during active SOJIA. Such a pattern has not been described for other inflammatory skin diseases nor did we find it in biopsies from nine patients with acute urticaria. It was accompanied by exclusive expression of MRP8, but not MRP14 by the secretory cells of sweat glands. Because MRP8 and MRP14, released by epithelial cells, exhibit pro-inflammatory effects on endothelial cells and leucocytes, the particular expression pattern of MRP8 and MRP14 in SOJIA is likely to represent a decisive early constitutive component in this inflammatory disease. Their differential expression further points to distinct roles of the individual molecules in inflammatory processes.

Arthritis, Juvenile↗

PubMed2004

Decorin deficiency leads to impaired angiogenesis in injured mouse cornea.

Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wild-type mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN.

Animals↗

PubMed2004

Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response.

Blood monocytes are well-characterized precursors for macrophages and dendritic cells. Subsets of human monocytes with differential representation in various disease states are well known. In contrast, mouse monocyte subsets have been characterized minimally. In this study we identify three subpopulations of mouse monocytes that can be distinguished by differential expression of Ly-6C, CD43, CD11c, MBR, and CD62L. The subsets share the characteristics of extensive phagocytosis, similar expression of M-CSF receptor (CD115), and development into macrophages upon M-CSF stimulation. By eliminating blood monocytes with dichloromethylene-bisphosphonate-loaded liposomes and monitoring their repopulation, we showed a developmental relationship between the subsets. Monocytes were maximally depleted 18 h after liposome application and subsequently reappeared in the circulation. These cells were exclusively of the Ly-6C(high) subset, resembling bone marrow monocytes. Serial flow cytometric analyses of newly released Ly-6C(high) monocytes showed that Ly-6C expression on these cells was down-regulated while in circulation. Under inflammatory conditions elicited either by acute infection with Listeria monocytogenes or chronic infection with Leishmania major, there was a significant increase in immature Ly-6C(high) monocytes, resembling the inflammatory left shift of granulocytes. In addition, acute peritoneal inflammation recruited preferentially Ly-6C(med-high) monocytes. Taken together, these data identify distinct subpopulations of mouse blood monocytes that differ in maturation stage and capacity to become recruited to inflammatory sites.

Animals↗

PubMed2004

The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice.

Mononuclear phagocytes can be used by intracellular pathogens to disseminate throughout the host. In the bloodstream these cells are generically referred to as monocytes. However, blood monocytes are a heterogeneous population, and the exact identity of the leukocyte(s) relevant for microbial spreading is not known. Experiments reported in this study used Listeria monocytogenes-infected mice to establish the phenotype of parasitized blood leukocytes and to test their role in systemic dissemination of intracellular bacteria. More than 90% of the blood leukocytes that were associated with bacteria were CD11b(+) mononuclear cells. Analysis of newly described monocyte subsets showed that most infected cells belonged to the Ly-6C(high) monocyte subset and that Ly-6C(high) and Ly-6C(neg-low) monocytes harbored similar numbers of bacteria per cell. Interestingly, systemic infection with wild-type or DeltaactA mutants of L. monocytogenes, both of which escape from phagosomes and replicate intracellularly, caused expansion of the Ly-6C(high) subset. In contrast, this was not evident after infection with Deltahly mutants, which neither escape phagosomes nor replicate intracellularly. Importantly, when CD11b(+) leukocytes were isolated from the brains of lethally infected mice, 88% of these cells were identified as Ly-6C(high) monocytes. Kinetic analysis showed a significant influx of Ly-6C(high) monocytes into the brain 2 days after systemic infection. This coincided with both bacterial invasion and up-regulation of brain macrophage chemoattractant protein-1 gene expression. These data indicate that the Ly-6C(high) monocyte subset transports L. monocytogenes into the brain and establish their role as Trojan horses in vivo.

Animals↗

PubMed2004

Senescent BALB/c mice are able to develop resistance to Leishmania major infection.

Aging has been associated with a decline in immunocompetence and resistance to infections, partially due to dysregulated NO production by macrophages and deficits in mounting Th2 cell responses. We wondered if these alterations would reverse the immune response in experimental leishmaniasis. Bone-marrow-derived macrophages from 2- and 18-month-old (senescent) C57BL/6 or BALB/c mice showed no marked difference in leishmanicidal functions. In vivo infections of resistant C57BL/6 mice with Leishmania major revealed no difference between senescent and young mice. However, among susceptible BALB/c mice, senescent animals showed less foot-pad swelling than young mice, and 40 to 60% of them even showed healing of ulcers, reduced parasite dissemination, and a Th1 cell response. These changes were associated with a spontaneous release of interleukin-12 (IL-12) by macrophages from aged but not from young mice. Since exogenous microbial stimulation can influence immune responses during aging, we also infected senescent mice who were raised under specific-pathogen-free (SPF) conditions. They showed neither resistance nor a Th1 response, but their macrophages still spontaneously released IL-12. A microbiological analysis showed that conventionally kept mice, but not SPF mice, had experienced infection with murine hepatitis virus (MHV), an infection associated with a Th1-like response. We conclude that for the reversal of the immune response, senescence is the premier requirement but needs to be completed by another mandatory event such as microbial stimulation. One of the age-related, but not environment-related, factors is the spontaneous release of IL-12 by macrophages, while confrontation with MHV presents an environment-related difference, with both having the potential to support a Th1 response.

Aging↗

PubMed2003

Chemotactic activity of S100A8 and S100A9.

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Animals↗

PubMed2003

CD4+ T cell-associated pathophysiology critically depends on CD18 gene dose effects in a murine model of psoriasis.

In a CD18 hypomorphic polygenic PL/J mouse model, the severe reduction of CD18 (beta(2) integrin) to 2-16% of wild-type levels leads to the development of a psoriasiform skin disease. In this study, we analyzed the influence of reduced CD18 gene expression on T cell function, and its contribution to the pathogenesis of this disease. Both CD4(+) and CD8(+) T cells were significantly increased in the skin of affected CD18 hypomorphic mice. But only depletion of CD4(+) T cells, and not the removal of CD8(+) T cells, resulted in a complete clearance of the psoriasiform dermatitis. This indicates a central role of CD4(+) T cells in the pathogenesis of this disorder, further supported by the detection of several Th1-like cytokines released predominantly by CD4(+) T cells. In contrast to the CD18 hypomorphic mice, CD18 null mutants of the same strain did not develop the psoriasiform dermatitis. This is in part due to a lack of T cell emigration from dermal blood vessels, as experimental allergic contact dermatitis could be induced in CD18 hypomorphic and wild-type mice, but not in CD18 null mutants. Hence, 2-16% of CD18 gene expression is obviously sufficient for T cell emigration driving the inflammatory phenotype in CD18 hypomorphic mice. Our data suggest that the pathogenic involvement of CD4(+) T cells depends on a gene dose effect with a reduced expression of the CD18 protein in PL/J mice. This murine inflammatory skin model may also have relevance for human polygenic inflammatory diseases.

Animals↗

PubMed2003

Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone.

Suppression of collagen synthesis is a major therapeutic goal in the treatment of fibrotic disorders. We show here that alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide well known for its pigment-inducing capacity, modulates collagen synthesis and deposition. Alpha-MSH in vitro suppresses the synthesis of collagen types I, III, and V and down-regulates the secretion of procollagen type I C-terminal peptide (PICP) in human dermal fibroblasts treated with the fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Alpha-MSH did not interfere with TGF-beta1 signaling, because TGF-beta1-induced expression of collagen mRNA was not affected, implying a posttranscriptional mechanism. Human dermal fibroblasts in vitro express a high affinity binding site for MSH, which was identified by reverse transcription PCR and immunofluorescence analysis as the melanocortin-1 receptor (MC-1R). Immunohistochemical studies on normal adult human skin confirmed MC-1R expression in distinct dermal fibroblastic cells. The MC-1R on fibroblasts appears to be functionally relevant because alpha-MSH increased the amount of intracellular cAMP, and coincubation with a synthetic peptide corresponding to the human Agouti signaling protein abrogated the inhibition of TGF-beta1-induced PICP secretion by alpha-MSH. To assess the in vivo relevance of these findings, a mouse model was used in which dermal fibrosis was induced by repetitive intracutaneous injections with TGF-beta1. The inductive activity of TGF-beta1 on collagen deposition and the number of dermal cells immunoreactive for vimentin and alpha-smooth muscle actin was significantly suppressed by injection of alpha-MSH. Melanocortins such as alpha-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders.

Actins↗

PubMed2003

Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of glomerulonephritis.

Expression of two S100 proteins, myeloid related protein (MRP)8 and MRP14, as well as their complex formation indicate proinflammatory properties of macrophages. We analyzed if the different forms of glomerulonephritis (GN) are associated with the appearance of certain phenotypes of infiltrating macrophages characterized by expression of MRP8 and MRP14 as well as their complex formation. Immunohistochemical analysis of 89 renal biopsies with different forms of nephritis revealed that expression and complex formation of MRP8 and MRP14 by infiltrating macrophages in the glomeruli correlated with the severity of the inflammatory process. As such, MRP8/MRP14-expressing monocytes prevailed in highly proliferating forms of GN, i.e., systemic lupus erythematosus GN and extracapillary GN. In contrast, a high percentage of macrophages in the renal interstitium expressed MRP8 and MRP14 without concomitant formation of their complex, and they indicated a chronic type of inflammatory reaction in GN. Immunosuppressive drugs had no direct effects on the expression of MRP8 and MRP14 in macrophages in vitro. The correlation of MRP8 and MRP14 expression with disease activity indicates that these calcium-binding proteins are of pathophysiological relevance in GN. In addition, our findings reflect differences in the inflammatory mechanisms underlying the various forms of GN, as they revealed that distinct macrophage subpopulations prevail in the different forms of GN.

Adult↗