Complement Proteins Are Present in Developing Endochondral Bone and May Mediate Cartilage Cell Death and Vascularization

Andrades, José A.; Nimni, Marcel E.; Becerra, José; Eisenstein, Reuben; Davis, M. Natalie; Sorgente, Nino

doi:10.1006/excr.1996.0269

Cited by 60 publications

(48 citation statements)

References 4 publications

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“…Immunohistochemical studies clearly indicated that complement was activated during enchondral ossification, possibly for the modulation of apoptosis (74,75). These studies indicated that some interaction of the complement system with bone cells exists.…”

Section: Complement and Bone Biologymentioning

confidence: 88%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

185

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Section: Complement and Bone Biologymentioning

confidence: 88%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

185

154

View full text Add to dashboard Cite

show abstract

“…Factor B, C3, C5, and C9 are associated with endochrondral bone formation and cartilage degradation (123). C1s can degrade collagens and gelatin present in human cartilage (124) and can activate matrix metalloproteinase-9, a protease with established roles in the metastasis of cancers (125)(126)(127).…”

Section: Complement Proteins Facilitate Invasion and Migrationmentioning

confidence: 99%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

220

249

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Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

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“…+ cells isolated from normal human bone marrow, using a modification of the techniques previously described by Andrades et al 40,41 The chambers were implanted subcutaneously into the backs of individual mice. Paired chambers were removed 1 month later and fixed for histological analysis, or opened and dissected for FACS, cytospin slide preparation, and immunohistochemistry.…”

mentioning

confidence: 99%

The number and generative capacity of human B lymphocyte progenitors, measured in vitro and in vivo, is higher in umbilical cord blood than in adult or pediatric bone marrow

Arakawa-Hoyt

Thiemann

et al. 1999

Bone Marrow Transplant

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The number and generative capacity of human B lymphocyte progenitors, measured in vitro and in vivo, is higher in umbilical cord blood than in adult or pediatric bone marrow Summary:The lack of human B lymphocyte development in beige/nude/XID (bnx) mice is in sharp contrast to the robust development observed in another immune deficient strain, the NOD/SCID mouse. The ability to generate human B lymphocytes in the NOD/SCID, but not bnx mouse has been hypothesized to be caused by differences in the microenvironments or systemic cytokine concentrations. In the current studies we report that the differences in development can be primarily attributed to the source of the progenitors transplanted into the mice. The prior studies in bnx mice used cultured pediatric or adult bone marrow (BM) as the source of the CD34 + cells, whereas the NOD/SCID studies have predominantly used fresh or cultured umbilical cord blood (UCB). We have analyzed BM and UCB for the number of human CD34 + /CD38 − cells capable of in vitro B lymphocyte development, and have found a lower frequency of B lymphocyte generation in BM. The individual B lymphocyte clones that developed from bone marrow produced 100-fold fewer cells than the UCB-derived clones. In agreement with the in vitro studies, human B lymphocytes developed in bnx mice from both CD34+ and CD34 + /CD38 − cells isolated from human umbilical cord blood, but not from equivalent numbers of CD34 + and CD34 + /CD38 − progenitors from bone marrow. Therefore, the lower generative capacity, and frequency of B lymphocyte precursors in human marrow may be responsible for the previous results that showed a lack of B lymphocyte development in bnx mice. Keywords: B lymphopoiesis; hematopoietic stem cells; CD34 ϩ progenitors; umbilical cord blood; bone marrowImmune deficient mouse xenograft systems are used to study the development of multilineage progeny from transplanted human hematopoietic stem and progenitor cells. The most successful murine strains used to date are the beige/nude/XID (bnx) and the NOD/LtSz-scid/scid (NOD/ scid). There are several differences in the two xenograft systems, including the mutations responsible for the murine immunodeficiencies, the duration of the engraftment assays that can be done, and the human hematopoietic lineages that develop. 1-13 The current report focuses on differences in development of human B lymphocytes from transplanted human hematopoietic stem and progenitor cells obtained from bone marrow vs umbilical cord blood, in the bnx/hu xenograft system. Reconstitution of the B lymphoid compartment after bone marrow transplantation can lag behind recovery of other hematopoietic lineages.14-16 Our studies indicate that human hematopoietic progenitors capable of reconstituting the B lymphocyte compartment in a xenogeneic transplant model (human to mouse) are scarce in human bone marrow, but comprise a higher percentage of human umbilical cord blood progenitors.We established a successful xenograft system using beige/nude/xid (bnx) mice as recipients of hu...

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Complement Proteins Are Present in Developing Endochondral Bone and May Mediate Cartilage Cell Death and Vascularization

Cited by 60 publications

References 4 publications

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Cancer and the Complement Cascade

The number and generative capacity of human B lymphocyte progenitors, measured in vitro and in vivo, is higher in umbilical cord blood than in adult or pediatric bone marrow

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