Fibrocytes

The following sections are included:

• CONTRIBUTORS

• CONTENTS

The following sections are included:

• Introduction

• Phenotypic Properties

• Functional Roles in Wound Repair

• Role in Health and Disease
  • Wound Repair
  • Tumor Biology
  • Immunostimulatory Properties
  • Infectious Diseases
  • Scleroderma
  • Nephrogenic Systemic Fibrosis (NSF)
  • Asthma, Acute Lung Injury, and Pulmonary Fibrosis

• Conclusions

• Acknowledgments

• References

The following sections are included:

• Introduction

• Requirement of T Cells for the Development of Fibrosis

• T Cell-mediated Fibrosis in Human Disease

• Fibrocytes

• Fibrocytes are Potent Antigen Presenting Cells

• Fibrocytes Secrete Type I Collagen and Inflammatory Cytokines

• Conclusion

• References

The following sections are included:

• Introduction

• Biology of the Monocyte-Macrophage System

• Differentiation of Monocytes into Cell Types Other than Macrophages

• Peripheral Blood Mononuclear Cells can also Differentiate into Fibroblast/Stromal Cells

• Soluble Factors that Regulate Fibrocyte Differentiation

• Regulation of Fibrocytes by Glucose and Insulin

• Regulation of Fibrocyte Differentiation by SAP and Aggregated IgG

• Regulation of Fibrocyte Differentiation by T cells and Extracellular Matrix

• Summary

• Acknowledgments

• References

The following sections are included:

• Introduction

• Fibroblast Precursors

• Clonal Transplantation

• HSC Origin of Fibroblasts

• Perspectives

• Acknowledgments

• References

The following sections are included:

• Introduction

• Altered Structure and Composition of the Extracellular Matrix of Hypertrophic Scars

• A Th2 Polarized Immune Response in Hypertrophic Scar

• Dysregulated Apoptosis in Hypertrophic Scar
  • Apoptosis in the Resolution of Inflammation
  • Delayed Fibroblast and Myofibroblast Apoptosis in Hypertrophic Scar

• Increased Levels of the Profibrotic Growth Factors TGF-β and CTGF in Hypertrophic Scar

• Hypertrophic Scarring is Associated with Blood Borne Fibrocytes

• Increased Numbers of Fibrocytes can be Cultured from the Blood of Burn Patients

• Establishment of LSP-I as a Fibrocyte Marker

• Increased Numbers of Fibrocytes in Post-burn Hypertrophic Scar

• Potential Interaction of Fibrocytes and Endothelial Cells

• Possible Interactions of Fibrocytes and Fibroblasts

• Elevated TGF-β and CTGF mRNA Levels in Burn Patient Fibrocytes

• Fibrocytes may Contribute to the Myofibroblast Population

• Possible Role of Fibrocytes in the Polarized Th2 Immune Response

• Proposed Role of Fibrocytes in Hypertrophic Scar Formation

• Summary and Prospects for FutureWork

• Acknowledgments

• References

Asthma is a chronic inflammatory disease of the airways characterized by structural and functional alterations of the bronchial epithelium and remodeling of the normal bronchial architecture. Bronchial myofibroblasts are thought to play a crucial role in the pathogenesis of subepithelial fibrosis, which represents a prominent feature of the remodeling process. Although it has been postulated for many years that myofibroblasts derive from tissue fibroblasts, recent studies have indicated that bone marrow-derived fibrocytes may contribute to the bronchial myofibroblast population in asthma and may be responsible for the excessive collagen deposition below the epithelial basement membrane. Investigating how fibrocytes emerge in asthmatic airways and what their fate is, may uncover key mechanisms involved in the pathogenesis of airway remodeling and may help clarify the functional role of the remodeling process in asthma.

Systemic sclerosis (SSc), also called scleroderma, is a fibrosing autoimmune disease. There are several different clinical types of SSc that have variable internal organ fibrosis and degrees of skin involvement with fibrosis. A prominent vasculopathy often precedes the onset of fibrosis. The origins of myofibroblasts which are the dominant matrix synthesizing cell in SSc involved tissue has traditionally been thought to arise from transformation of resident fibroblasts left over from embryonic development in response to cytokine/growth factor stimulation from activated T cells and monocytes that populate areas of fibrosis in SSc organs. We have evidence that the blood mononuclear cells generate large numbers of fibroblast-like cells when they are cultured with an auto antigen for SSc, type I collagen. Development of myofibroblasts from epithelial mesenchymal transition (EMT), pericytes and fibrocytes are discussed as possible contributors to fibrosis in SSc. Implication of alternative sources of myofibroblasts in SSc from the traditionally held view of their development from resident fibroblasts for therapeutic approaches is discussed.

It is now over a decade since Bucala and colleagues first described a population of cells in circulation with fibroblast-like properties that were involved in tissue repair. Since that time we have learned a significant amount about these bone marrow-derived cells that are now termed “fibrocytes,” and which contribute to wound healing and fibrosis. These cells express leukocyte markers such as CD34, CD45 and CD13, and have also been demonstrated to express mesenchymal markers such as procollagens I and III, vimentin and fibronectin. In addition, they have also been shown to express the chemokine receptors, CXCR4 and CCR7 that appear to be important in cellular trafficking from the vascular to the extravascular compartment. Fibrocytes have been shown to contribute to a number of fibrotic disorders, and here we review their involvement in lung diseases including pulmonary fibrosis, asthma and vascular remodeling.

Fibrosis is a characteristic pathological feature of progressive organ diseases, resulting in organ failure. Renal fibrosis is a progressive and potentially lethal disease caused by diverse clinical entities. The degree of renal fibrosis well correlates with the prognosis of renal diseases independent of their etiologies. Fibrocytes are peculiar circulating cells that share markers of leukocytes as well as mesenchymal cells. A considerable number of fibrocytes dual positive for CD45 and type I collagen or CD34 and type I collagen infiltrated the interstitium along with progression of fibrosis in an experimental murine renal fibrosis model. Most fibrocytes in the kidneys were positive for CCR7. In addition, a ligand for CCR7, secondary lymphoid tissue chemokine (SLC/CCL21) co-localized with high endothelial venule-like vessels in fibrotic kidneys. CCL21/CCR7 blockade reduced the number of infiltrating fibrocytes as well as the extent of renal fibrosis, which was confirmed by a decrease in renal transcripts of pro a1 chain of type I collagen and transforming growth factor-β₁. These findings suggest that fibrocytes contribute to the progressive renal fibrosis dependent on CCL21/CCR7 signaling.

The following sections are included:

• Introduction

• Atherosclerosis: The PerpetualWound
  • Inflammation: Fatty Core Development
  • Tissue Formation/Remodeling: Development of the Fibrous Cap
  • Plaque Rupture
  • TGF-β: The Key Factor

• Fibrocytes: Friend or Foe in Atherosclerosis

• Monocytes: A Source of Fibrocytes

• Intimal Hyperplasia

• Conclusion

• References

The following sections are included:

• Introduction

• Historical Context

• The Affected Population
  • Renal Disease
  • Dialysis
  • Renal transplantation
  • Other Comorbidities
    • Hypercoagulability, thrombosis, and endothelial injury
    • Other systemic processes

• Presentation
  • Signs, Symptoms and Progression
  • Diagnosis
    • Laboratory investigation
    • Biopsy and histopathology
    • Ancillary studies
  • Treatment
    • Renal transplantation
    • Extracorporeal photopheresis (ECP)
    • Plasmapheresis
    • Other considerations

• Discussion
  • Circulating Fibrocytes
    • A basic conceptual model and possible triggers
    • The newest suspect: Endothelin-I
    • Fibrosis via accretion — a proposal
    • Fibrosis via exogenous substances — an alternate hypothesis

• Acknowledgment

• References

The following sections are included:

• Introduction

• Normal CD34⁺ Fibrocytes — Morphology

• CD34⁺ Fibrocytes in the Carcinoma-associated Stroma

• Pathogenesis of CD34⁺ Fibrocyte Loss

• Diagnostic Significance of CD34⁺ Fibrocytes

• Tumors Histogenetically Linked to CD34⁺ Fibrocytes
  • Solitary FibrousTumor (SFT)
  • Dermatofibrosarcoma Protuberans (DFSP)

• Stromal Tumors of the Breast

• LipomatousTumors
  • Miscellaneous Tumors
  • Gastrointestinal Stromal Tumors

• Concluding Remarks and Future Perspectives

• References

The following sections are included:

• INDEX