Methods: We investigated the cell types showing an immunohistochemical reaction for FXIII-A in tissue samples of infectious, malignant, and non-infectious/malignant granulomatous skin lesions by using double labeling immunohistochemical reactions for various immune cell specific markers to answer whether macrophages and/or dendritic cells are labeled for FXIII-A. Moreover, we also aimed to match these histological findings with the results of our in vitro experiments on human blood derived monocytes that were differentiated into macrophages or dendritic cells in the presence of various activators.
Results: In all of the samples of the examined diseases FXIII-A was exclusively expressed by macrophages, however depending on the activation pathway of the macrophages the expression of FXIII-A was not obligate. While macrophages expressing other markers of alternative activation, responsible for extra cellular matrix remodeling and wound healing were FXIII-A+, the classically activated ones with a primary role in the host versus pathogen interactions were negative. These findings were also confirmed by our in vitro experiments using different cytokine stimuli of the two activation pathways.
Conclusions: Presence of FXIII-A expressing macrophages is not a disease specific marker but indicates a possible common mechanism in their activation. Therefore, the relation of FXIII-A to disease development and progression in various diseases depends more likely on the specific tissue environment than on the presence of FXIII-A+ macrophages.