Systemic and intestinal levels of factor XIII-A: the impact of XXXX on expression in macrophage subtypes.

@entity1 @entity32 @entity469 @entity31 @entity11772
BACKGROUND: Subunit A of coagulation factor XIII (FXIII-A) is important for clot stability and acts in the subsequent wound healing process. Loss of plasma FXIII-A has been reported after surgery, sepsis, and inflammatory conditions. In the intestinal mucosa, FXIII-A is expressed by macrophages and cellular FXIII-A has been associated with phagocytosis and migration of macrophages. The objective was to evaluate the consequences of intestinal @entity32 on resident mucosal macrophages, focusing on the level and distribution of FXIII-A. METHODS: Plasma and colonic biopsies were collected from 67 @entity1 with @entity31 and controls. Intestinal samples were stained using immunohistochemistry for FXIII-A and macrophages ( @entity469 , @entity11772 and iNOS). In situ hybridization were used to assess the intestinal expression of FXIII-A. FXIII-A antigen and activity levels were measured in plasma. RESULTS: Increased infiltration of @entity469 positive macrophages in the inflamed mucosa coincided with increased extracellular deposited FXIII-A and decreased expression and intracellular protein levels of FXIII-A. A decreased proportion of FXIII-A/ @entity469 / @entity11772 triple-positive macrophages was observed in inflamed mucosa, indicating a reduction of the M2 phenotype with consequent loss of FXIII-A. No induction of iNOS positive macrophages was observed. Stimulation of na  ve monocytes with physiological concentrations of pro-inflammatory mediators negatively affected the expression of FXIII-A. Measurements in plasma confirmed the loss of both FXIII antigen and activity during active disease. CONCLUSIONS: Intestinal @entity32 in UC induces loss of M2 macrophages with subsequent loss of FXIII-A synthesis. The loss of cellular FXIII-A may impact migration and phagocytosis, and hence limit pathogen eradication in UC.
