Home  About us  Contact
 

Macrophage Depletion (macrophage + depletion)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007
W. H. Kitchens
Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 × BALB/c)F1 recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30,80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis. [source]

Partial depletion of macrophages by ED7 reduces renal injury in Adriamycin nephropathy

NEPHROLOGY, Issue 5 2005
YIPING WANG
SUMMARY: Background: Because macrophages are considered to be possible effectors of disease in Adriamycin (ADR) nephrosis, we hypothesized that depletion of macrophages might protect against the initiation of renal injury. In the present study, a monoclonal antibody (ED7) directed against CD11b/CD18 integrin, which is expressed by macrophages, was used to investigate the pathogenetic effects of macrophages in ADR nephropathy. Methods: Male Wistar rats were treated with ED7 antibody, starting 1 day prior to ADR (7.5 mg/kg) treatment, or 7 days post-ADR when overt proteinuria was established. Results: Circulating ED7-positive cells were reduced by approximately 30% in rats with ADR nephrosis by the ED7 antibody, while the number of macrophages in the renal cortex of ADR rats was reduced by nearly 50% with the ED7 treatment, whether administered before or after ADR. Creatinine clearance was significantly ameliorated by ED7 when commenced pre-ADR (P < 0.05), but not when commenced post-ADR (P = NS) in comparison to untreated ADR rats. However, proteinuria was not alleviated by either ED7 treatment. Morphometric analysis showed less glomerular sclerosis when ED7 was commenced pre-ADR compared with ADR alone (P < 0.01), but not when commenced post-ADR (P = NS). Tubular atrophy was reduced by ED7 when it was commenced pre-ADR (tubular cell height and tubular diameter: P < 0.01 and P < 0.001, respectively), as was interstitial expansion (P < 0.01) compared with ADR alone. Cortical macrophage infiltration was reduced by 50% compared with ADR alone by the ED7 commenced before or after ADR. The number of cortical CD4+ T cells fell with ED7 starting pre-ADR, but not with the ED7 treatment commencing after ADR. Conclusion: Partial macrophage depletion starting before but not after ADR protected both renal function and structure in this model of chronic proteinuric renal disease. [source]

Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007
W. H. Kitchens
Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 × BALB/c)F1 recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30,80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis. [source]

Muscle resident macrophages control the immune cell reaction in a mouse model of notexin-induced myoinjury

ARTHRITIS & RHEUMATISM, Issue 1 2010
Madly Brigitte
Objective Skeletal muscle may be the site of a variety of poorly understood immune reactions, particularly after myofiber injury, which is typically observed in inflammatory myopathies. This study was undertaken to explore both the cell dynamics and functions of resident macrophages and dendritic cells (DCs) in damaged muscle, using a mouse model of notexin-induced myoinjury to study innate immune cell reactions. Methods The myeloid cell reaction to notexin-induced myoinjury was analyzed by microscopy and flow cytometry. Bone marrow (BM) transplantation studies were used to discriminate resident from exudate monocyte/macrophages. Functional tests included cytokine screening and an alloantigenic mixed leukocyte reaction to assess the antigen-presenting cell (APC) function. Selective resident macrophage depletion was obtained by injection of diphtheria toxin (DT) into CD11b,DT receptor,transgenic mice transplanted with DT-insensitive BM. Results The connective tissue surrounding mouse muscle/fascicle tissue (the epimysium/perimysium) after deep muscle injury displayed a resident macrophage population of CD11b+F4/80+CD11c,Ly-6C,CX3CR1, cells, which concentrated first in the epimysium. These resident macrophages were being used by leukocytes as a centripetal migration pathway, and were found to selectively release 2 chemokines, cytokine-induced neutrophil chemoattractant and monocyte chemoattractant protein 1, and to crucially contribute to massive recruitment of neutrophils and monocytes from the blood. Early epimysial inflammation consisted of a predominance of Ly-6ChighCX3CR1lowCD11c, cells that were progressively substituted by Ly-6ClowCX3CR1high cells displaying an intermediate, rather than high, level of CD11c expression. These CD11cintermediate cells were derived from circulating CCR2+ monocytes, functionally behaved as immature APCs in the absence of alloantigenic challenge, and migrated to draining lymph nodes while acquiring the phenotype of mature DCs (CD11c+Ia+CD80+ cells, corresponding to an inflammatory DC phenotype). Conclusion The results in this mouse model show that resident macrophages in the muscle epimysium/perimysium orchestrate the innate immune response to myoinjury, which is linked to adaptive immunity through the formation of inflammatory DCs. [source]