Résumé
This study was aimed to investigate the influence of TLR2 and TLR4 agonists on the migration and adhesion activity of umbilical cord blood (UCB) CD34(+) cells and to explore the underlying mechanism. The expression of TLR2 and TLR4 on UCB CD34(+) cells was detected with flow cytometry. The effect of TLR2 agonist (PAM3CSK4) and TLR2 agonist (LPS) on the migration and adhesion ability of UCB CD34(+) cells was evaluated with chemotaxis and adhesion assays. The results indicated that expression levels of TLR2 and TLR4 were (14.2 ± 3.8)%, (19.6 ± 4.1)% respectively. Compared with the control group, the migration activity of UCB CD34(+) cells toward SDF-1 decreased significantly in LPS group (p < 0.01). The adhesion activity was not altered significantly in LPS group. However, both the migration activity towards SDF-1 and the adhesion activity of UCB CD34(+) cells were not changed significantly in PAM3CSK4 group. Further study found that LPS did not affect the expression level of CXCR4 on CD34(+) cells, but could inhibit the spontaneous migration ability of CD34(+) cells. It is concluded that TLR4 activation can decrease the chemotaxis function of CD34(+) cells towards SDF-1, which may associate with the decreased spontaneous migration ability of CD34(+) cells.
Sujets)
Humains , Antigènes CD34 , Sang , Mouvement cellulaire , Cellules cultivées , Chimiokine CXCL12 , Sang foetal , Biologie cellulaire , Allergie et immunologie , Lipopeptides , Pharmacologie , Lipopolysaccharides , Pharmacologie , Récepteur de type Toll-2 , Récepteur de type Toll-4Résumé
CD47, also known as integrin-associated protein (IAP), is an immunoglobulin-like protein. It can inhibit the phagocytosis of macrophages through binding with signal-regulatory protein alpha chain of inhibitory receptor on macrophage (SIRPα). The expression of CD47 on normal hematopoietic stem cells (HSCs) is useful for maintaining the stability of HSCs in body, but the high expression of CD47 existed on leukemia stem cell (LSCs) of AML patients which can reduce the macrophage-induced phagocytosis to LSCs and decrease the clearance of innate immune system of organism to LSCs. In this article, the expression and function of CD47 on HSCs and LSCs as well as the role of CD47 in the prognosis and target therapy of AML are reviewed.