Modulation of fibroblast proliferation by postsurgical macrophages

Fukasawa, Manabu; Bryant, Simon M.; Nakamura, Robert M.; diZerega, Gere S.

doi:10.1016/0022-4804(87)90124-7

Cited by 38 publications

(12 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The earliest cellular response following surgical implantation of a tendon graft in a bone tunnel most likely involves accumulation of inflammatory cells. It is likely that macrophages play an important role in tendon healing since these cells function to scavenge cellular debris following injury and they can release growth factors that induce extracellular matrix synthesis [13] and stimulate fibroblasts or other stem cells to proliferate [5]. Previous studies of wound healing in other tissues clearly indicate that macrophage accumulation is an early event in the healing process [21].…”

Section: Introductionmentioning

confidence: 99%

Macrophages accumulate in the early phase of tendon–bone healing

et al. 2005

View full text Add to dashboard Cite

A scar tissue interface forms rather than a normal ligament insertion site following attachment of a tendon graft to bone. The specific cell types that initiate the process of tendon-to-bone healing are unknown. We hypothesized that inflammatory cell accumulation following tendon-to-bone repair results in this scar interface. We used a rodent model to examine the temporal and spatial pattern of accumulation of hematopoietic lineage cells in the early phase of tendon-to-bone healing. Thirty-six Lewis rats underwent anterior cruciate ligament (ACL) reconstruction in the left knee using a flexor digitorum longus tendon graft. Six animals were sacrificed at 4, 7, 11, 14, 21, and 28 days after surgery. Serial sections were analyzed for proliferating cells (PCNA), recruited macrophages (ED1 ), resident macrophages (ED2), neutrophils, T-lymphocytes (CD3), mast cells, immature progenitor cells/pericytes (expressing the NG2 cell-surface chondroitin sulfate proteoglycan), and newly-formed blood vessels (Factor VIII). Neutrbphils, EDlt and ED2+ macrophages accumulated sequentially in the healing tendon graft, with progressive cell ingrowth from the interface towards the inner tendon. Neutrophils and EDl+ cells were seen in the tendon-bone interface at 4 days after surgery, while ED2+ macrophages were not identified until 11 days. These cells progressively repopulated the tendon graft. NG2-positive progenitor cells were found along the edge of the bone tunnel in the interface, but these cells did not invade the tendon. Occasional T-lymphocytes and mast cells were seen in the tendon-bone interface. There was no proliferation of intrinsic tendon cells, indicating that the tendon does not directly contribute to healing. We hypothesize that cytokines produced by infiltrating macrophages are likely to contribute to the formation of a fibrous scar tissue interface rather than a normal insertion site.

show abstract

Section: Introductionmentioning

confidence: 99%

Macrophages accumulate in the early phase of tendon–bone healing

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Macrophage populations become then the predominant subsets of cells until the end of the inflammatory process. Activated macrophages can release growth factors that induce extracellular matrix synthesis [ 131, inhibit extracellular matrix degradation [15] and stimulate fibroblasts or other stem cells to proliferate [9].…”

Section: Introductionmentioning

confidence: 99%

Neutrophils and macrophages accumulate sequentially following Achilles tendon injury

Marsolais

Côté

Frenette

2001

Journal Orthopaedic Research

135

119

View full text Add to dashboard Cite

Structural damage and inflammation occur following tendon injury. The purpose of this study was to determine the time course of inflammatory cell accumulation in two animal models of acute tendinopathy. In the first model, rat Achilles tendons were exposed by blunt dissection, injected with collagenase and sacrificed at I , 3, 7, 14 and 38 days. In the second model, collagenase was injected percutaneously and rats were sacrificed after I and 3 days. Sham animals were sacrificed at 1 and 3 days in both models. Neutrophil and ED1' macrophage populations increased by 46-and 1 %fold, respectively, after 1 day in surgically exposed Achilles tendons (EAT) injected with collagenase. Neutrophils dropped by 70'1.0 while the concentration of ED1 + macrophages remained constant at day 3 post-injury. Neutrophils and ED1 macrophages returned to control values after 7 and 14 days, respectively. ED?' macrophages showed a tendency to increase at day 38 although no significant difference was observed relative to ambulatory controls. Collagenase injected percutaneously reduced the extent of inflammation compared with operated animals. Thus, injured tendons exhibited a specific sequence of inflammatory cell accumulation which varied in intensity according to the modality used for collagenase injection. 0 100 1

show abstract

“…1 Following the initial recruitment of neutrophils to the site of injury, an accumulation of macrophages is observed in the tendon ECM within the first 24 h. 6 Macrophages participate in the phagocytic removal of necrotic debris, but eventually shift their function to promote fibroblast proliferation and guide ECM remodeling through the release of chemotactic and growth factors. 2,5,7,8 Macrophages have two general phenotypes--classically activated pro-inflammatory macrophages (M1) that promote ECM breakdown, inflammation, and apoptosis; and alternatively activated anti-inflammatory macrophages (M2) that coordinate ECM deposition and tissue repair. 9,10 Previous work in damaged skeletal muscle has demonstrated that suppression of either M1 or M2 macrophage function severely impairs tissue regeneration, indicating the important balance between inflammation and regeneration for proper tissue repair.…”

mentioning

confidence: 99%

Changes in macrophage phenotype and induction of epithelial‐to‐mesenchymal transition genes following acute Achilles tenotomy and repair

Sugg

Lubardic

Gumucio

et al. 2014

Journal Orthopaedic Research

121

135

View full text Add to dashboard Cite

Tendon injuries occur frequently in physically active individuals, but the clinical outcomes for these injuries can be poor. In many injured tissues the repair process is orchestrated by two types of cells, macrophages and fibroblasts. Macrophages, which have both proinflammatory (M1) and antiinflammatory (M2) phenotypes, can directly participate in tissue remodeling and direct the response of other cells through the secretion of cytokines and growth factors. In many organ systems, epithelial cells can transdifferentiate into fibroblasts, which can then regenerate damaged ECM. This process is triggered via activation of epithelial-to-mesenchymal transition (EMT) signaling programs. Most tendons are surrounded by sheets of epithelial cells, and these tissue layers could provide a source of fibroblasts to repair injured tendons. To gain greater insight into the biology of tendon repair, we performed a tenotomy and repair in Achilles tendons of adult rats and determined changes in macrophage phenotype, and ECM- and EMT-related genes over a four week time course. The results from this study suggest that changes in macrophage phenotype and activation of EMT-related programs likely contribute to the degradation and subsequent repair of injured tendon tissue.

show abstract

Modulation of fibroblast proliferation by postsurgical macrophages

Cited by 38 publications

References 20 publications

Macrophages accumulate in the early phase of tendon–bone healing

Macrophages accumulate in the early phase of tendon–bone healing

Neutrophils and macrophages accumulate sequentially following Achilles tendon injury

Changes in macrophage phenotype and induction of epithelial‐to‐mesenchymal transition genes following acute Achilles tenotomy and repair

Contact Info

Product

Resources

About