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Abstract Background Monocytes are involved in tumor growth and metastasis, but the distribution of monocyte phenotypes and their role in the development of malignant pleural effusion (MPE) remains unknown. Methods A total of 94 MPE patients (76 diagnosed with adenocarcinoma lung cancer and 18 with squamous cell lung cancer) and 102 volunteers for health examination in Xiangya Hospital from December 2016 to December 2019 were included in the study. Results The distribution of monocyte subtypes identified by the expression of CD14 and CD16 were analyzed by flow cytometry. The proportion of CD14++CD16+ intermediate monocytes were significantly increased in pleural effusion of MPE patients. The complement system components were assayed by immunohistochemistry and ELISA, and higher expression of the classical and alternative pathways were detected in malignant pleural tissue. Transwell assay further revealed that C5a enhanced the infiltration of intermediate monocytes into the pleural cavity by promoting CCL2 production in pleural mesothelial cells (PMCs). In addition, C5a promoted the secretion of IL‐1β by intermediate monocytes. Furthermore, C5a activated in intermediate monocytes and IL‐1β released after C5a stimulation by monocytes promoted the proliferation, migration, adhesion, and epithelial‐to‐mesenchymal transition (EMT) of tumor cells, and attenuated tumor cell apoptosis. Conclusions C5a, activated by the classical and alternative pathways of the complement system, not only mediated the infiltration of intermediate monocytes by enhancing CCL2 production in PMCs but also induced IL‐1β release from the recruited monocytes in MPE. The consequence of C5a activation and the subsequent IL‐1β overexpression in intermediate monocytes contributed to MPE progression.

Abstract Background Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV. Methods Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA. Results We observed decreased percentages of CD4+ and CD8+ T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3+ T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the TEM17 cell frequency, with concomitant increases in the frequencies of CD4+ TEM1 and CD4+ TEM17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8+ T cells and CD4+ TEM subsets were correlated with renal prognosis and inflammatory markers. Conclusions Our data indicate that dysregulated chemokine receptor expression on CD4+ and CD8+ effector memory T cells and aberrant distribution of functional CD4+ T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.

BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.

Background: Monocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear. Methods: 30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay. Results: Compared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys. Conclusion: Enhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV. [ABSTRACT FROM AUTHOR]

The aim of this study was to detect virulence genes and drug resistance genes in pathogenic Escherichia coli (E.coli) isolated from diarrhea calves feces and to detect drug resistance phenotypes, and genotypic. As a result, a total of 22 strains of E.coli were separated and identified, but only 18 strains were pathogenic. The virulence gene test showed that the LT, Stx1, F5, F6, and irp2 gene detection rate were 66.67% (12/18), 16.67% (3/18), 55.56% (10/18), 44.44% (8/18) and 16.67% (3/18), respectively. Antibiotic susceptibility tests showed that the isolates were susceptible to Kanamycin and Florfenicol and resistant to Cefalotin (94.44%) and the like. Resistance gene tet (A), gryA, parC, sulI, sulII, sulIII, blaTEM, blaCTX-m, blaSHV, aac (3)-II, aac (6 ')-Ib and rmtB detection rate are 77.78% (14/18), 44.44% (8/18), 55.56% (10/18), 22.22% (4/18), 11.11% (2/18), 11.11% (2/18), 77.78 % (14/18), 5.56% (1/18), 44.44% (8/18), 50% (9/18), 55.56% (10/18), and 27.78% (5/18), respectively. ERIC-PCR (repetitive intergenic consensus-polymerase chain reaction) classified 18 pathogenic E.coli into 4 distinct genotypes, and all strains carrying the LT virulence gene were brought together, but there was no link between drug resistance genes and genotypic. The results of this study provids experimental evidence for the prevention, control pathogenic E. coli disease in calves. [ABSTRACT FROM AUTHOR]