Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression

• Published in: Kidney international Vol. 54; no. 6; pp. 2170 - 2183
• Main Authors: Li, Fu Keung, Davenport, Andrew, Robson, Rachel L., Loetscher, Pius, Rothlein, Robert, Williams, John D., Topley, Nicholas
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.12.1998; Nature Publishing
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies - pharmacology; Biological and medical sciences; C-C chemokines; C-x-C chemokines; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokine CCL5 - genetics; Chemokine CCL5 - metabolism; Chemokines - metabolism; Dactinomycin - pharmacology; Emergency and intensive care: renal failure. Dialysis management; Epithelial Cells - metabolism; Epithelial Cells - physiology; Humans; inflammation; Intensive care medicine; Intercellular Adhesion Molecule-1 - metabolism; Intercellular Adhesion Molecule-1 - pharmacology; Interleukin-1 - pharmacology; Interleukin-8 - genetics; Interleukin-8 - immunology; Interleukin-8 - metabolism; leukocyte trafficking host defence; Leukocytes - physiology; Medical sciences; mesothelium; Monocytes - physiology; Neutrophils - physiology; peritoneal dialysis; Peritoneum - cytology; Peritoneum - metabolism; Peritoneum - physiology; peritonitis; RNA, Messenger - metabolism; mesothelium; leukocyte trafficking host defence; peritonitis; inflammation; peritoneal dialysis; C-C chemokines; C-x-C chemokines; Kidney disease; Human; Cell culture; Urinary system disease; Pathophysiology; Intercellular adhesion molecule 1; Leukocyte; Migration; Peritoneal dialysis; Chemokine; Extrarenal dialysis; Chronic; Treatment; Abdominal disease; Renal failure; Complication; Peritonitis; Peritoneum
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1046/j.1523-1755.1998.00174.x

Leukocyte migration across human peritoneal mesothelial cells is dependent on directed chemokine secretion and ICAM-1 expression. Leukocyte migration into the peritoneal cavity is a diagnostic feature of peritonitis in patients treated with peritoneal dialysis (PD). While neutrophil (PMN) influx is characteristic of the acute phase of peritoneal infection, significant mononuclear cell (MNC) infiltration, occurs throughout the whole period of infection. Recent data suggests that human peritoneal mesothelial cell (HPMC) adhesion molecule expression and the synthesis of chemotactic cytokines may be important in the process. In the present study we have examined, the regulation and directed secretion of chemokines (IL-8, MCP-1 and RANTES) and the basolateral to apical migration of unstimulated leukocytes across mesothelial cell monolayers using an in vitro model where HPMC were grown on the porous membrane of tissue culture inserts. Separate experiments have defined the importance of chemokine synthesis and ICAM-1 expression in the transmigration process. Apical stimulation of HPMC with IL-1β or TNFα resulted in a time and dose dependent up-regulation of IL-8, MCP-1 and RANTES mRNA expression and synthesis. This secretion was predominately into the apical compartment (>85%) with all chemokines. Apical pre-stimulation of HPMC resulted in a dose- and time-dependent migration of both PMN and MNC across HPMC. Neutrophil migration was significantly reduced in the presence of appropriate concentrations of polyclonal IL-8 antibody (IL-1β (100pg/ml) 153 ± 12 versus anti-IL-8 (100ng/ml) 71 ± 7 (× 103) PMN, N = 6, P < 0.02) and in the presence of anti-ICAM-1 F(ab)′2 fragments or soluble ICAM-1. Constitutive and cytokine stimulated mononuclear cell migration was significantly reduced in the simultaneous presence of polyclonal MCP-1 or RANTES antibody. These data demonstrate that HPMC synthesize IL-8, MCP-1 and RANTES in response to inflammatory cytokines. HPMC-derived C-x-C and C-C chemokines might contribute to the intra-peritoneal recruitment of leukocytes during peritoneal inflammation.