Possible role of factor XIII subunit A in Fcgamma and complement receptor-mediated phagocytosis.
Besides its traditional role in hemostasis, factor XIII subunit A (FXIII-A) is supposed to function as a cellular transglutaminase and to be involved in certain intracellular processes, including cytoskeletal remodeling. To investigate its intracellular role, the aim of the present study was to follow changes in FXIII-A production in combination with the receptor-mediated phagocytic activities of monocytes/macrophages and to examine the phagocytic functions of monocytes in patients with FXIII-A deficiency. Human blood monocytes were isolated from the buffy coats of healthy volunteers and cultured for 4 days. The FcgammaR-mediated phagocytosis of sensitized erythrocytes (EA) and the complement receptor (CR)-mediated phagocytosis of complement-coated yeast particles were studied during monocyte/macrophage differentiation. Changes in the gene expression of FXIII-A were detected by real-time quantitative RT-PCR. FXIII-A protein production was investigated with fluorescent image analysis at single cell level and Western immunoblot analysis. Both the FcgammaR and CR-mediated phagocytosis increased during culturing, which peaked on day 3. The phagocytic activity of the cells could be markedly inhibited with monodansylcadaverine, an inhibitor of the transglutaminase-induced crosslinking of proteins. The phagocytosis of EA, complement-coated and uncoated yeast particles was found to be strongly diminished in monocytes of FXIII-A deficient patients. The phagocytic functions of cultured cells showed a change in parallel with the alterations in FXIII-A mRNA expression, as well as with that in FXIII-A in protein synthesis detected by image and Western immunoblot analyses in concert. Our results suggest that FXIII-A plays a role in the Fcgamma and complement receptor-mediated phagocytic activities of monocytes/macrophages.
Sárváry
Attila
A
Department of Preventive Medicine, School of Public Health, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen H-4012, P.O. Box 9, Hungary.
Szucs
Sándor
S
Balogh
Imre
I
Becsky
Aron
A
Bárdos
Helga
H
Kávai
Mária
M
Seligsohn
Uri
U
Egbring
Rudolf
R
Lopaciuk
Stanislaw
S
Muszbek
László
L
Adány
Róza
R
D015153:Blotting, Western; D002103:Cadaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology; D005176:Factor XIII / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000502:physiology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017463:Receptors, Complement 3b / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000378:metabolism
D004791:Enzyme Inhibitors; D017463:Receptors, Complement 3b; D017452:Receptors, IgG; C064015:factor XIII subunit A; D012313:RNA; D005176:Factor XIII; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine