Opposite effects of thrombospondin-1 via CD36 and CD47 on homotypic aggregation of monocytic cells.
Thrombospondin-1 (TSP-1), an extracellular matrix protein, has a multimodular structure and each domain specifies a distinct biological function through interaction with a specific ligand. In this study we found that exogenously added TSP-1 inhibits phorbol myristate acetate (PMA)/LPS-induced homotypic aggregation of human monocytic U937 cells, whereas the 70-kDa fragment of TSP-1 generated by the proteolytic cleavage of the intact molecule promotes the homotypic aggregation. The aggregation was also inhibited by anti-CD47 mAb or the 4N1K peptide, of which sequence is derived from the CD47-binding site of TSP-1 and absent in the 70-kDa fragment. In contrast, the augmented cell aggregation by the 70-kDa fragment was hampered by anti-CD36 mAb or antibody against the CD36-binding site of TSP-1. The cell aggregation of U937 cells was completely blocked, even in the presence of the 70-kDa fragment, by mAb against leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). We therefore propose that TSP-1 may regulate LFA-1/ICAM-1-mediated cell adhesion of monocytes/macrophages by either the inhibitory effect through CD47 or the promoting effect through CD36 depending on which domain/fragment is functional in a given biological setting.
Yamauchi
Yasushi
Y
Department of Biochemistry, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Kuroki
Motomu
M
Imakiire
Takayuki
T
Uno
Koichi
K
Abe
Hironori
H
Beppu
Richiko
R
Yamashita
Yuichi
Y
Kuroki
Masahide
M
Shirakusa
Takayuki
T
D015703:Antigens, CD / Q000502:physiology*; D018955:CD36 Antigens / Q000502:physiology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D015703:Antigens, CD; D018955:CD36 Antigens; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D019700:Thrombospondin 1; D018799:Intercellular Adhesion Molecule-1