Effects of inhibitors of C1q biosynthesis on macrophage Fc receptor subclass-mediated antibody-dependent cellular cytotoxicity and phagocytosis |
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| Authors: | R Mocharla H Mocharla R W Leu |
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| Affiliation: | 1. Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China;2. Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, Shandong, PR China;3. Department of Dermatology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China;4. Department of Burn and Plastic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, PR China;1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China;2. Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China;3. Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China;1. Department of Electronic Engineering, Chang Gung University, Guishan Dist., 33302, Taoyuan, Taiwan;2. Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Guishan Dist., 33305, Taoyuan, Taiwan;3. Department of Electronic Engineering, Ming Chi University of Technology, Taishan Dist., 24301, New Taipei City, Taiwan;1. College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019, China;2. College of Medicine, Shaoxing University, Shaoxing, 312000, China;1. Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai 200241, China;2. Songjiang District Center for Animal Disease Control and Prevention, Shanghai 201699, China;3. College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China |
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| Abstract: | We examined the effects of the inhibitors of C1q or collagen biosynthesis, 2,2'-dipyridyl (DP), and 3,4-dehydro-DL-proline (DHP) on murine macrophage (M phi) FcR subclass-mediated antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis of sheep erythrocyte targets. Oil-elicited peritoneal M phi from C3HeB/FeJ mice which were cultured for 24 hr with DP (0.08 or 0.10 mM) or DHP (0.8 or 1.0 mM) showed a significant decrease in FcR subclass-mediated ADCC for murine monoclonal IgG2a (FcRI) and IgG2b/IgG1 (FcRII) as well as for heterologous polyclonal IgG. These collagen inhibitors also blocked phagocytosis mediated by both IgG2a- and IgG2b-opsonized erythrocytes. DP was more potent than DHP in blocking FcR effector functions in a reversible fashion and neither inhibitor affected M phi C3b receptor function. Pretreatment of M phi with collagenase resulted in significant reduction in FcR-mediated ADCC and phagocytosis. The inhibition of M phi FcR subclass-mediated ADCC and phagocytosis by collagen C1q synthetic inhibitors or by collagenase treatment further confirms a functional relationship between cell-associated C1q and FcR-dependent functions. |
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