Lysophosphatidic acid (LPA) is a bioactive phospholipid that regulates physiological and pathological processes in numerous cell biological functions, including cell migration, apoptosis, and proliferation. Macrophages are found in most human tissues and have multiple physiological and pathological functions. There is growing evidence that LPA signaling plays a significant role in the physiological function of macrophages and accelerates the development of diseases caused by macrophage dysfunction and inflammation, such as inflammation-related diseases, cancer, atherosclerosis, and fibrosis. In this review, we summarize the roles of LPA in macrophages, analyze numerous macrophage- and inflammation-associated diseases triggered by LPA, and discuss LPA-targeting therapeutic strategies.

In patients, endometrial hyperplasia (EH) is often accompanied by abnormal uterine bleeding (AUB), which is prone to release large amounts of heme. However, the role of excess heme in the migration and infiltration of immune cells in EH complicated by AUB remains unknown. In this study, 45 patients with AUB were divided into three groups: a proliferative phase group (n = 15), a secretory phase group (n = 15) and EH (n = 15). We observed that immune cell subpopulations were significantly different among the three groups, as demonstrated by flow cytometry analysis. Of note, there was a higher infiltration of total immune cells and macrophages in the endometrium of patients with EH. Heme up-regulated the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2) in endometrial epithelial cells (EECs) in vitro, as well as chemokine (e.g., CCL2, CCL3, CCL5, CXCL8) levels. Additionally, stimulation with heme led to the increased recruitment of THP-1 cells in an indirect EEC-THP-1 co-culture unit. These data suggest that sustained and excessive heme in patients with AUB may recruit macrophages by increasing the levels of several chemokines, contributing to the accumulation and infiltration of macrophages in the endometrium of EH patients, and the key molecules of heme metabolism, HO-1 and Nrf2, are also involved in this regulatory process.