Objective: To observe the change in expression of Toll-like receptor 4 (TLR4) of splenic macrophage in patients with hypersplenism due to portal hypertension (PH), and investigate the role of TLR4 of splenic macrophage in hypersplenism.
Methods: Splenectomy was performed on 20 patients with hypersplenism due to PH (hypersplenism group) and 6 patients with rupture of spleen by trauma (control group) and the specimens of spleen were collected. The splenic macrophages were isolated by adhibit wall method. The expression of TLR4 of splenic macrophage was detected by immunohistochemical method (SABC), and the result was analyzed by the image analysis system. The phagocytosis of splenic macrophage was measured by chicken red blood cell (CRBC) phagocytosis assay. The level of serum endotoxin was detected before the operation by limulus assay. The results of these 2 groups were compared, and correlation analysis was made among different results of the hypersplenism group.
Results: The expression of TLR4 of splenic macrophage was 109 +/- 32 in the hypersplenism group, significantly higher than that of the control group (62 +/- 5, P < 0.01). The rate of phagocytosis and index of phagocytosis of splenic macrophage in the hypersplenism group were 12.6% +/- 3.0% and 0.146 +/- 0.035 respectively, both significantly higher than those of the control group (6.9% +/- 0.5% and 0.076 +/- 0.008 respectively, both P < 0.01) The level of endotoxin of the hypersplenism group was 0.28 EU/ml +/- 0.21 EU/ml, significantly higher than that of the control group (0.054 EU/ml +/- 0.014 EU/ml, P < 0.05). The rate of phagocytosis and the index of phagocytosis of splenic macrophage were notably positively correlated with the expression of TLR4 (r = 0.601, P < 0.01 and r = 0.553, P < 0.05), and the level of endotoxin (r = 0.724 P < 0.01 and r = 0.506, P < 0.05). The expression of TLR4 of splenic macrophage was positively correlated with the level of endotoxin (r = 0.525, P < 0.05).
Conclusion: The expression of TLR4 of splenic macrophage in patients with hypersplenism due to PH was increased significantly. It may be one of the important factors of hypersplenism due to PH that "endotoxemia-->increase of expression of TLR4 of splenic macrophage (activation of TLR of splenic macrophage)-->increased destruction of red blood cells by macrophage".