The Expression Patterns of Peritoneal Defensins

Abstract

Background Local defense mechanisms are important for the integrity of the peritoneum, but few details are known about the expression patterns of antimicrobial proteins such as human defensin in normal and damaged peritoneum. Methods Part A: The expression of different defensins in normal ( n = 12), inflamed ( n = 5), and metastatic peritoneum ( n = 4) and in cultured human peritoneal mesothelial cells was analyzed using mRNA and immunohistochemistry. Part B: Using immunohistochemistry the expression of different defensins was analyzed in different subgroups: healthy controls ( n = 25), patients with chronic appendicitis ( n = 25) or acute appendicitis ( n = 10), and end-stage renal disease patients ( n = 25, with 15 on peritoneal dialysis). Results Part A: Human neutrophil peptides (HNP) 1 and 3 and human β-defensins (HBD) 1 to 3 mRNA were detected in peritoneal specimens. In addition, HNP1,3, HBD1, HBD2, and HBD3 proteins were detected using immunohistochemistry. Part B: HBD1 showed a constitutive expression in mesothelium, while HBD2 and HNP1,3 were associated with inflammation. Decreased expressions of HNP1,3 were observed in end-stage renal disease patients and in patients on peritoneal dialysis. Conclusions For the first time, the expression patterns of defensins in normal and damaged peritoneum have been described. The reduced expression of some defensins in end-stage renal disease is of potential clinical interest against the background of the frequent infective complications seen in peritoneal dialysis.

Pathophysiological Changes to the Peritoneal Membrane during PD-Related Peritonitis: The Role of Mesothelial Cells

“…Many are constitutively expressed by resident cells and stored in secretory granules, whereas others are induced upon proinflammatory stimuli. Defensins are a group of antimicrobial peptides that are produced by mesothelial cells and cells of the innate immune system in response to bacterial infection [ 155 , 156 ]. These peptides are activated in the presence of bacteria and act by disrupting the lipid membranes of bacteria.…”

The Peritoneum: Beyond the Tissue – A Review

“…The peritoneum is generally described as a protective barrier and frictionless interphase that covers abdominal viscera ( Herrick and Mutsaers, 2004 ; Mutsaers, 2004 ; Yung et al, 2006 ; Susan and Tak Mao, 2012 ), but it is a much more complex structure with a great variety of functions. Besides from participating in the embryogenesis of primitive gut ( Burn and Hill, 2009 ), peritoneal functions include: selective fluid and cell transport ( Mutsaers, 2002 , 2004 ; Susan and Tak Mao, 2012 ; Retana et al, 2015 ; van Baal et al, 2017 ); physiological barrier ( Davies et al, 1990 ; Heel and Hall, 1996 ; Zarrinkalam et al, 2001 ; Grupp et al, 2007 ; Kazancioglu, 2009 ; Susan and Tak Mao, 2012 ); immune induction, modulation, and inhibition ( Bird et al, 2004 ; Susan and Tak Mao, 2012 ; van Baal et al, 2017 ); tissue repair and scarring ( Susan and Tak Mao, 2012 ; van Baal et al, 2017 ); preventing adhesion and tumoral dissemination ( Mutsaers, 2002 , 2004 ); and trans -cellular migration (see Figure 5 ) ( Mutsaers, 2002 ; Herrick and Mutsaers, 2004 ; Yung et al, 2006 ; Wang et al, 2010 ; van Baal et al, 2017 ).…”

“…The peritoneal fluid separates both layers of mesothelium with a quantity of 5–100 ml in volume ( Blackburn and Stanton, 2014 ; van Baal et al, 2017 ). It is described as an ultra-filtrated blood derivate ( Heel and Hall, 1996 ; Blackburn and Stanton, 2014 ), containing immune elements like complement’s C3, C4 ( Heel and Hall, 1996 ; Tang et al, 2004 ), and immunoglobulin G ( Davies et al, 1990 ); antimicrobial peptides like Human neutrophil peptide (HNP) 1 and 3, and Human β defensins (HβD) 1 to 3 ( Zarrinkalam et al, 2001 ; Grupp et al, 2007 ); immune cells like macrophages, lymphocytes, eosinophils, mesothelial cells and mast cells ( van Baal et al, 2017 ). All these humoral elements are produced by mesothelial cell ( Zarrinkalam et al, 2001 ; Tang et al, 2004 ; Grupp et al, 2007 ) (see Table 2 ), and along with the cellular components, make the peritoneal fluid a physiological barrier against infection.…”

Biocompatible Peritoneal Dialysis: The Target Is Still Way Off

“…The peritoneum maintains local homeostasis and provides protection from movement-induced frictions and adhesions by secretion of phospholipids, mainly phosphatidylcholine, together with surfactant proteins (SP-A, -B, -C) (Hills et al., 1998). In steady state, mesothelial cells produce 5–100 ml of peritoneal fluid containing complement factors (Tang et al., 2004; Zelek et al., 2016), immunoglobulins (Davies et al., 1990), defensins (Grupp et al., 2007), and immune cells like macrophages, lymphocytes, eosinophils, and mast cells (van Baal et al., 2017) that exert anti-infectious actions and regulate the inflammatory response (Isaza-Restrepo et al., 2018). In vitro , mesothelial cells migrate in an AQP-1-dependent manner (Ryu et al., 2012; Zhai et al., 2012), suggesting efficient wound healing capacity of superficial peritoneal erosions.…”