Three different cell types can synthesize factor XIII subunit A in the human liver.

The origin of human Factor XIII subunit A (FXIII A) has been a subject of intense speculation and investigation during the last decade. The major question under dispute is whether hepatocytes can produce this clotting factor. Experimental evidence obtained by FXIII A phenotype analysis in bone marrow transplant patients clearly identified hemopoietic cells (monocytes/macrophages and/or megakaryocytes/ platelets) as a source of FXIII A, and also showed that additional extra-hemopoietic site(s) of synthesis also exist. The liver has been suggested as a possible extra-hemopoietic source of plasma FXIII A, but the cells responsible for synthesizing FXIII A were not identified yet. Our present study was designed to determine the cellular distribution of both FXIII A and its encoding mRNA in human liver samples by using light- and electron-microscopic immuno-morphological and in situ hybridization techniques. In paraformaldehyde/glutaraldehyde (PA/GA) fixed, araldite-embedded semithin sections that were immunostained by an ABC/DAB based postembedding immunocytochemical method, FXIII A could be detected in Kupffer cells, connective tissue histiocytes and hepatocytes. Immunoreactive hepatocytes were observed almost exclusively around the venae centrales. By using postembedding immunogold labeling, FXIII A could be electron-microscopically visualized in these hepatocytes in the immediate vicinity of the lamellae of the endoplasmic reticulum. By in situ hybridization using a mixture of five 32-40mer biotinylated oligonucleotides (ONs) to mRNA regions encoded by exons VI, XI and XV and a labeling system containing streptavidin conjugated with alkaline phosphatase/BCIP/NBT, the message for FXIII A could be detected in the same cell types. These results show that in human liver three different types of cells can synthesize FXIII A, but the extent of their contribution to the plasma FXIII A level will require further studies.