Sterile Injury Repair and Adhesion Formation at Serosal Surfaces

Abstract

Most multicellular organisms have a major body cavity containing vital organs. This cavity is lined by a mucosa-like serosal surface and filled with serous fluid which suspends many immune cells. Injuries affecting the major body cavity are potentially life-threatening. Here we summarize evidence that unique damage detection and repair mechanisms have evolved to ensure immediate and swift repair of injuries at serosal surfaces. Furthermore, thousands of patients undergo surgery within the abdominal and thoracic cavities each day. While these surgeries are potentially lifesaving, some patients will suffer complications due to inappropriate scar formation when wound healing at serosal surfaces defects. These scars called adhesions cause profound challenges for health care systems and patients. Therefore, reviewing the mechanisms of wound repair at serosal surfaces is of clinical importance. Serosal surfaces will be introduced with a short embryological and microanatomical perspective followed by a discussion of the mechanisms of damage recognition and initiation of sterile inflammation at serosal surfaces. Distinct immune cells populations are free floating within the coelomic (peritoneal) cavity and contribute towards damage recognition and initiation of wound repair. We will highlight the emerging role of resident cavity GATA6+ macrophages in repairing serosal injuries and compare serosal (mesothelial) injuries with injuries to the blood vessel walls. This allows to draw some parallels such as the critical role of the mesothelium in regulating fibrin deposition and how peritoneal macrophages can aggregate in a platelet-like fashion in response to sterile injury. Then, we discuss how serosal wound healing can go wrong, causing adhesions. The current pathogenetic understanding of and potential future therapeutic avenues against adhesions are discussed.

A functional PVA aerogel-based membrane obtaining sutureability through modified electrospinning technology and achieving promising anti-adhesion effect after cardiac surgery

“…Adhesion is the body's excessive repair of tissue damage to some extent. Besides the aforementioned role of fibroblasts, they are also involved with the recruitment and activation of inflammatory cells [ 44 , 45 ]. Therefore, the anti-inflammatory effect of different materials was evaluated via the proliferation and differentiation of monocytes and the inflammatory factors secretion.…”

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation

“…The inflammatory response at the damaged site is one of the mechanisms that causes adhesion formation, which stimulates the exudation of a large number of inflammatory mediators from the peritoneum or intestinal wall, further stimulating the exudation and deposition of fibrin in the damaged area and leading to the formation of dense adhesions [ 4 ]. Second, the inflammatory response affects the normal repair of peritoneal mesothelial cells, promotes the transformation of mesothelial cells to mesenchymal cells, and contributes to adhesion formation [ 5 ].…”

“…Previous studies have identified that intraperitoneal adhesion formation contains several mutual interactive and overlapping processes such as coagulation and fibrinolysis, inflammation, cell proliferation, and fibrosis [ 3 ]. Multifarious cell types such as immunocytes (such as macrophages, monocytes, and mast cells), fibroblasts, and mesothelial cells are involved in the above process [ 4 ]. It is recently suggested that the severity of inflammation is closely and positively correlated with adhesion formation.…”

Endogenously-Produced Hyaluronan and Its Potential to Regulate the Development of Peritoneal Adhesions

“…MCs modulate inflammation by synthesis and release of HA, which is able to sequester free radicals and initiate tissue repair responses [ 5 ]. Further, if HA and other extracellular matrix components constitutively present in the extracellular space are modified by injuries, they can become damage-associated molecular patterns—immune-stimulatory molecular patterns that can induce inflammation in case of sterile injury, recognized by CD44 receptor and others [ 4 , 5 ]. Moreover, failure to remove HA degradative products from sites of injury results in unremitting inflammation [ 31 ].…”

“…The mesothelial-to-mesenchymal transition (MMT) consists of gradual loss of epithelial characteristics and the acquisition of myofibroblast-like phenotype. Subsequently, deposition of extracellular matrix (ECM) by myofibroblasts is induced and fibrotic tissue is formed among visceral organs [ 3 , 5 ].…”