Cell barrier function of resident peritoneal macrophages in post-operative adhesions

Ito, Tomoya; Shintani, Yusuke; Fields, Laura; Shiraishi, Manabu; Podaru, Mihai‐Nicolae; Kainuma, Satoshi; Yamashita, Kizuku; Kobayashi, Kosaku; Perretti, Mauro; Lewis-McDougall, Fiona; Suzuki, Ken

doi:10.1038/s41467-021-22536-y

Cited by 43 publications

(28 citation statements)

References 55 publications

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“…Changes in macrophage dynamics, in particular the loss of F4/80 high cavity resident macrophages after surgery, has previously been reported with C57BL/6 mice ( 25 ). However, specific differences between BALB/c and C57BL/6 mice have not been investigated; hence we performed a more in-depth characterization of the dynamic changes in peritoneal macrophage subsets following surgery in the two strains.…”

Section: Resultssupporting

confidence: 58%

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

et al. 2022

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Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus, effective treatments are not forthcoming. Peritoneal macrophages accumulate after surgery and previous studies have attributed either pro- or anti-scarring properties to these cells. We propose that there are complex and nuanced responses after surgery with respect to both resident and also monocyte-derived peritoneal macrophage subpopulations. Moreover, we contend that differences in responses of specific macrophage subpopulations in part explain the risk of developing peritoneal scars. We characterized alterations in peritoneal macrophage subpopulations after surgery-induced injury using two strains of mice, BALB/c and C57BL/6, with known differences in macrophage response post-infection. At 14 days post-surgery, BALB/c mice displayed more adhesions compared with C57BL/6 mice. This increase in scarring correlated with a lower influx of monocyte-derived macrophages at day 3 post-surgery. Moreover, BALB/c mice showed distinct macrophage repopulation dynamics after surgery. To confirm a role for monocyte-derived macrophages, we used Ccr2-deficient mice as well as antibody-mediated depletion of CCR2 expressing cells during initial stages of adhesion formation. Both Ccr2-deficient and CCR2-depleted mice showed a significant increase in adhesion formation associated with the loss of peritoneal monocyte influx. These findings revealed an important protective role for monocyte-derived cells in reducing adhesion formation after surgery.

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Section: Resultssupporting

confidence: 58%

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

et al. 2022

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“…Much of the transcriptional and functional behaviour of cavity macrophages is driven by retinoid X receptors and the transcription factor GATA6 in response to local production of the vitamin A metabolite retinoic acid [6][7][8][9]. Despite playing key roles in many peritoneal diseases [1,[10][11][12][13] our understanding of the cellular interactions that regulate the identity and maintenance of these macrophages remains incomplete.…”

Section: Introductionmentioning

confidence: 99%

Cell origin and niche availability dictate the capacity of peritoneal macrophages to colonize the cavity and omentum

et al. 2022

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The relationship between macrophages of the peritoneal cavity and the adjacent omentum remains poorly understood. Here, we describe two populations of omental macrophages distinguished by CD102 expression and use an adoptive cell transfer approach to investigate whether these arise from peritoneal macrophages, and whether this depends upon inflammatory status, the origin of peritoneal macrophages and availability of the omental niches. We show that whereas established resident peritoneal macrophages largely fail to migrate to the omentum, monocyte‐derived resident cells readily migrate and form a substantial component of omental CD102+ macrophages in the months following resolution of peritoneal inflammation. In contrast, both populations had the capacity to migrate to the omentum in the absence of endogenous peritoneal and omental macrophages. However, inflammatory macrophages expanded more effectively and more efficiently repopulated both CD102+ and CD102− omental populations, whereas established resident macrophages partially reconstituted the omental niche via recruitment of monocytes. Hence, cell origin determines the migration of peritoneal macrophages to the omentum and predisposes established resident macrophages to drive infiltration of monocyte‐derived cells.

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“…Changes in macrophage dynamics, in particular the loss of F4/80 high cavity resident macrophages after surgery, has previously been reported with C57BL/6 mice [24]. However, specific differences between BALB/c and C57BL/6 mice have not been investigated; hence we performed a more in-depth characterisation of dynamic changes in peritoneal macrophage subsets following surgery in the two strains.…”

Section: Resultsmentioning

confidence: 90%

“…Similarly, two recent studies suggested that rapid recruitment of F4/80 high peritoneal resident macrophages to the site of mesothelial injury may result in the creation of a barrier preventing excessive fibrin attachment and consequently preventing the formation of adhesions after surgery (25, 35). We found that C57BL/6 mice showed a significantly higher number of peritoneal F4/80 high resident macrophages prior and at day 3 post-surgery compared with BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

Sahputra

Dejyong

Woolf

et al. 2022

Preprint

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Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus effective treatments are not forthcoming. Peritoneal macrophages accumulate after surgery and previous studies have attributed either pro- or anti-scarring properties to these cells. We propose that there are complex and nuanced responses after surgery with respect to both resident and monocyte-derived peritoneal macrophage subpopulations. Moreover, we contend that differences in responses of specific macrophage populations, in part, explain the risk of developing peritoneal scars. We characterised alterations in peritoneal macrophage subpopulations after surgery-induced injury using two strains of mice, BALB/c and C57BL/6, with known differences in macrophage response post-infection. At 14 days post-surgery, BALB/c mice displayed more adhesions compared with C57BL/6 mice. This increase in scarring correlated with a lower influx of monocyte-derived macrophages at day 3 post-surgery. Moreover, BALB/c mice showed distinct macrophage repopulation dynamics after surgery. To confirm a role for monocyte-derived macrophages, we used Ccr2-deficient mice as well as antibody-mediated depletion of CCR2 expressing cells during initial stages of adhesion formation. Both Ccr2-deficient and CCR2-depleted mice showed a significant increase in adhesion formation associated with the loss of a peritoneal monocyte influx. These findings reveal an important protective role for monocyte-derived cells in reducing adhesion formation after surgery.

show abstract

Cell barrier function of resident peritoneal macrophages in post-operative adhesions

Cited by 43 publications

References 55 publications

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

Cell origin and niche availability dictate the capacity of peritoneal macrophages to colonize the cavity and omentum

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

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