Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths, posing a serious threat to women′s health worldwide. At present, although the prognosis of some patients with breast cancer has improved, the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis. CD36 is a multiligand transmembrane glycoprotein expressed on various cell types. In recent years, studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells; promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues; regulate the function of Treg cells, CD8+ T cells, DCs, and other immune cells, and thus promote tumor development. In addition, CD36 is also associated with breast cancer stem cells, metastasis-initiating cells, and breast drug resistant cells. Therefore, CD36 could be an important potential therapeutic target for breast cancer.

Objective:To observe the effect of peripheral 5-hydroxytryptophan (5-HT)-induced neutrophil extracellular trap (NET) on lung injury in septic mice.Methods:Wild-type (WT type) and Tph1 knockout (KO) C57 mice (6-8 weeks) were selected and divided into WT mice sham group, WT mice sepsis group, Tph1 KO mice sham group and Tph1 KO mice sepsis group according to the random number table method. Mice in the sham group received sham surgery (only open the abdominal cavity to flip the cecum without ligation and puncture, and then close the abdominal cavity); the mice in the sepsis group received cecal ligation and puncture (CLP) to establish sepsis model. The mice were sacrificed 12 hours after the operation, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in bronchialalveolar lavage fluid (BALF) were detected by enzyme linked immunoadsordent assay (ELISA); at the same time, the lung tissues were collected, and the pathological changes of lung tissues were observed under light microscope, and the production of NET in lung tissues was observed by immunofluorescence microscope. Results:The pathological results suggested that the lung tissue structure in sham groups was intact without exudation, while the alveolar structures of mice in the sepsis groups were damaged, with obvious exudation in the alveolar cavity and thickened alveolar walls accompanied by a large number of inflammatory cell infiltration, and the degree of lung injury in the sepsis group of WT mice was more severe than that of the sepsis group of Tph1 KO mice. ELISA results showed that there was no statistically significant difference in the contents of TNF-α and IL-6 in mice BALF from different strains of the sham group; while the contents of TNF-α and IL-6 in BALF of septic mice group were significantly higher than those in sham group [WT mice: TNF-α (μg/L) was 158.20±28.46 vs. 14.00±3.28, IL-6 (μg/L) was 304.98±21.78 vs. 57.70±12.30; Tph1 KO mice: TNF-α (μg/L) was 85.88±20.13 vs. 14.95±1.53, IL-6 (μg/L) was 169.50±45.61 vs. 55.05±12.68, all P < 0.01], and the above index levels in the sepsis group of WT mice were significantly higher than the sepsis group of Tph1 KO mice [TNF-α (μg/L): 158.20±28.46 vs. 85.88±20.13, IL-6 (μg/L): 304.98±21.78 vs. 169.50±45.61, both P < 0.01]. Immunofluorescence staining showed that a very small amount of NET formation was detected in the mice lungs from the sham group; a large amount of NET formation was detected in the lung tissues in the sepsis group, which were significantly higher than those in sham group [WT mice: (34.75±7.27)% vs. (1.75±0.96)%, Tph1 KO mice: (14.25±5.74)% vs. (2.50±1.29)%, both P < 0.01], and the amount of NET produced in the lung tissues of the WT mice sepsis group was significantly higher than that of the Tph1 KO mice sepsis group [(34.75±7.27)% vs. (14.25±5.74)%, P < 0.01]. Conclusions:In sepsis, the increased production of inflammatory factors in the mice lung tissues induces to lung injury. The mechanism may relate to the increased production of NET in the lung tissues mediated by peripheral 5-HT synthesized by enterochromaffin cells and released into the blood; inhibiting the production of 5-HT in the peripheral blood can effectively reduce the production of NET in the lung tissues, thereby reducing lung injury.