The Globular Heads of C1q Specifically Recognize Surface Blebs of Apoptotic Vascular Endothelial Cells

Navrátil, J; Watkins, Simon C.; Wisnieski, Jeffrey J.; Ahearn, Joseph M.

doi:10.4049/jimmunol.166.5.3231

Cited by 237 publications

(164 citation statements)

References 65 publications

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“…It is also likely that MBL may exert its effects differentially in the peripheral and lung compartments; a 'double edged sword effect'. This may be due to the unique ability of alveolar macrophages to retain very high concentrations of certain mediators (eg, macrolide antibiotics) when compared to plasma concentrations 30 .…”

Section: Discussionmentioning

confidence: 99%

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Hodge

Dean

Hodge

et al. 2011

The Journal of Heart and Lung Transplantation

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Short running title: Decreased efferocytosis and MBL in BOSwith BOS) and 14 healthy controls. Abstract & Manuscript 2Results: In plasma, MBL levels were highly variable (0-17.538 g/mL), but increased in infected subjects vs control (p=0.09) or stable groups (p=0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time post-transplant. In BAL, MBL levels were less variable (0-73.3 ng/mL) and significantly reduced in patients with BOS vs controls and stable groups. 3Lung transplantation is now recognized as an effective treatment option for a variety of end-stage lung diseases and is associated with improvements in life expectancy and quality of life. However the five-year survival is currently only around 60%, the worst of any solid organ transplant, with death beyond the acute phase being largely due to progressive and treatment refractory airway remodeling (obliterative bronchiolitis, OB) manifest clinically as bronchiolitis obliterans syndrome (BOS). BOS is thought to follow persistent alloreactive, infective, and non-specific epithelial injury with dysregulated epithelial repair 1 . Although the predominant histopathologic finding in patients with OB is of fibro-proliferative small airway obliteration, large airways are also affected with the eventual development of bronchiectasis, leading directly to patient morbidity and mortality.The well-ordered process of apoptosis is important for regulation and maintenance of normal tissue homeostasis. During resolution of airway inflammation, apoptotic epithelial cells are removed by phagocytosis by alveolar macrophages (a process termed 'efferocytosis'). The pathological concept of failed efferocytosis has been described in regard to a number of lung diseases including pulmonary fibrosis 2 , cystic fibrosis 3 chronic granulomatous disease 4 smokers and patients chronic obstructive pulmonary disease (COPD) 5-8 .It is considered that the failed efferocytosis results in a net increase in apoptotic material that may lead to secondary necrosis of this material resulting in increased tissue damage and chronic inflammation. This was clearly shown in our studies of COPD where we found evidence of secondary necrosis (increased lactate dehydrogenase in BAL) and that the increased numbers of apoptotic bronchial epithelial cells negatively correlated with efferocytosis 6,9 . In lung transplant recipients we have also described an accumulation of apoptotic material associated with an increase in the cytotoxic mediator granzyme b in the airways 10,11 .Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis and is thus likely to be important in protecting against lung tissue damage. In other inflammatory chronic lung diseases including COPD, we have shown reduced levels of MBL that correlated with a defect in the 4 ability of alveolar macrophages to phagocytose apoptotic bronchial epithelial cells (efferocytosis) 8 . We further showed that treatm...

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Section: Discussionmentioning

confidence: 99%

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Hodge

Dean

Hodge

et al. 2011

The Journal of Heart and Lung Transplantation

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“…These C1q family members have extremely diverse functions, such as acting like hormones (Maeda et al, 2002;Takamatsu et al, 1993), contributing to the interaction of the cell with extracellular matrices (Tom Tang et al, 2005), recognizing targets for several immunological processes (Navratil et al, 2001), or connecting a single calcified otolith to the sensory epithelium (Murayama et al, 2002). On the other hand, TNF family members have been revealed to be involved in vertebrate oogenesis, but no data on the involvement of C1q family member in the process were reported.…”

Section: Discussionmentioning

confidence: 99%

Identification of a C1q family member associated with cortical granules and follicular cell apoptosis in Carassius auratus gibelio

Mei

Chen

Yue

et al. 2008

Molecular and Cellular Endocrinology

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“…The other hypothesis, known as "waste disposal hypothesis", supports the role of complement in the processing and clearance from the body of dying cells and/or immune complexes [30]. In support of this hypothesis, C1q has been shown to bind directly to apoptotic cells [31,32], an excess of apoptotic bodies was observed in the kidneys of C1qa -/-mice [3], and peritoneal macrophages from C1qa -/-mice displayed a defective clearance of apoptotic cells in vivo [4]. Here we provide additional support to this hypothesis by demonstrating that restoration of C1q levels with BMT rectified the defective clearance of apoptotic cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice

et al. 2004

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C1q deficiency in both humans and mice is strongly associated with autoimmunity. We have previously shown that bone marrow transplantation (BMT) restored C1q levels in C1q-deficient (C1qa(-/-)) mice. Here, we studied the effect of BMT on autoimmunity in C1qa(-/-) mice. Following irradiation, young C1qa(-/-) or wild-type MRL/Mp mice received bone marrow cells (BMC) from strain-matched wild-type or C1qa(-/-) animals. C1q levels increased rapidly when C1qa(-/-) mice received BMC from wild-type mice. Conversely, they decreased slowly in wild-type mice transplanted with C1qa(-/-) BMC. C1qa(-/-) animals transplanted with C1qa(-/-) BMC demonstrated accelerated disease when compared with wild-type mice given wild-type BMC. In contrast, a significant delay in the development of autoantibodies and glomerulonephritis was observed in C1qa(-/-) mice reconstituted with wild-type BMC, and the impaired clearance of apoptotic cells, previously described in C1qa(-/-) mice, was rectified. Moreover, the autoimmune disease was accelerated in wild-type mice given C1qa(-/-) BMC compared to animals transplanted with wild-type cells. These results provide supporting evidence that BMT may be a therapeutic option in the treatment of autoimmunity associated with human C1q deficiency

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The Globular Heads of C1q Specifically Recognize Surface Blebs of Apoptotic Vascular Endothelial Cells

Cited by 237 publications

References 65 publications

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Identification of a C1q family member associated with cortical granules and follicular cell apoptosis in Carassius auratus gibelio

Restoration of C1q levels by bone marrow transplantation attenuates autoimmune disease associated with C1q deficiency in mice

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