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Collagen VI (CVI) antibodies regulate macrophages differentiation through FcgammaRIIb signal transduction pathway
Author(s) -
Li Zhonghao,
Zhao Ming
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03847
Subject(s) - mapk/erk pathway , signal transduction , p38 mitogen activated protein kinases , syk , microbiology and biotechnology , kinase , chemistry , immunology , cancer research , biology , tyrosine kinase
We previously reported that monoclonal antibody against collagen VI (CVI mAb) regressing atherosclerotic plaque through inducing the shift of macrophage differentiation, namely from M1 to M2, and ensuing the macrophages engulf the plaque lipids and transfer the lipids to HDL through restoring lipid transfer protein ABCA1 expression. Here we report the cellular signal transduction on the CVI mAb inhibition of oxLDL‐induced M1 differentiation. Using purified human CD14 + cells, we find that oxLDL induces M1 differentiation is JNK and ERK MAPKs dependent. And CVI mAb inhibits M1, while activates M2 differentiation, though oxLDL also activates M2 differentiation in some way, but the M1/M2 ratio are significantly reversed by CVI mAb. The molecular mechanism behind these is that CVI mAb activates macrophage FcgammaRIIb and its downstream SHIP and Dok phosphatases, and inhibits Syk and Ras signal transduction pathway, which are MAPKs upstream kinases, so that CVI mAb inhibits ERK, JNK, and p38 MAPKs activation, and ensuing M1 differentiation. Thus, we found the signal transduction pathway of CVI mAb inhibition of oxLDL‐induced M1 differentiation: CVI mAb→FcgammaRIIb→SHIP→Dok→Syk and Ras→ERK and JNK MAPKs→M1. These results might give a new clue on control the lipids‐induced inflammatory reaction on the large blood vessel and therapeutic method to prevent atherosclerosis. Support or Funding Information This work was supported by the National Natural Science Foundation of China (grants 81772074, 81974045), the Natural Science Foundation of Guangdong, China (grant 2012B050600002), the Guangdong Province Talent Recruitment Foundation and the Guangdong Innovative Research Team Program (No. 201001Y0104675344), Project of Guangzhou city scientific plan (201804020002).