Polar Production of Interleukin‐8 by Mesothelial Cells Promotes the Transmesothelial Migration of Neutrophils: Role of Intercellular Adhesion Molecule–1

Abstract

Migration of polymorphonuclear neutrophils (PMNL) from the vascular compartment into the pleural space occurs rapidly during the development of parapneumonic effusions. This study investigated the polarized secretion of interleukin (IL)-8 in activated pleural mesothelial cells (PMC) and the migration of PMNL across resting, activated PMC monolayers. Results show that PMC produce IL-8 in a polar manner. When PMC were stimulated with Staphylococcus aureus or IL-1beta at the basal or at the apical surface, significantly (P< .05) more IL-8 was released toward the apical surface. This polarized production of IL-8 was confirmed by in situ hybridization. PMNL migration was higher from the basilar to apical than from the apical to basilar surface of PMC. Neutralizing antibodies against IL-8 and intercellular adhesion molecule (ICAM)-1 significantly (P< .001) blocked PMNL migration across activated monolayers. Thus, during pleural inflammation, PMC regulate the influx of PMNL into the pleural space by polar production of IL-8 and expression of ICAM-1.

Pleural Mesothelial Cells Express Both BLT2 and PPARα and Mount an Integrated Response to Pleural Leukotriene B4

“…LTB 4 is able to interact with two cell-surface receptors (BLT1 and BLT2) and with a nuclear receptor called PPAR␣. The interaction of LTB 4 with cell-surface receptors induces LTB 4 -mediated inflammatory activities while the interaction with PPAR␣ induces the catabolism of LTB 4 and, in turn, limits LTB 4 -correlated inflammation (2).…”

“…The underlying cellular and molecular events involved in the movement of neutrophils across the mesothelium into the pleural cavity are not completely elucidated. Furthermore, it is not known whether LTB 4 , released during the early events of inflammation, contributes to the adhesiveness of mesothelial cells and whether mesothelial cells are responsive to LTB 4 in a tightly controlled manner. The aims of the present study were to evaluate whether: 1) mesothelial cells express the cell-surface receptors for LTB 4 (BLT1 and BLT2), as well as the nuclear receptor for LTB 4 (PPAR␣); 2) LTB 4, and parapneumonic pleural fluids (PF) modulate the adhesion between pleural mesothelial cells and neutrophils and whether this phenomenon is associated to the modulation of ICAM-1 expression on pleural mesothelial cells; and 3) the modulation of the ICAM-1 expression is related to the activation of specific transcription factors.…”

“…In brief, mesothelial cells were seeded in 96-well plates at half-confluency and kept for 18 h alone, with synthetic LTB 4 , with PF supernatants, and with PFs supernatants in the presence of anti-BLT2 receptor or of anti-PPARa receptor. Peripheral blood neutrophils were isolated as previously described (1), labeled for 30 min with 20 M of fluorocromic dye CMFDA (Molecular Probes), and added at the concentration 1 ϫ 10 4 to the mesothelial layer for 20 min to promote adherence.…”

“…4 Because it has been previously demonstrated that LTB 4 is present in exudative pleural effusions and acts as a potent chemotactic agent for neutrophils during pleural inflammation (1), it was first evaluated whether primary mesothelial cells expressed proinflammatory cell-surface LTB 4 receptors and/or antiinflammatory nuclear LTB 4 receptor . Mesothelial cells coexpressed the anti-inflammatory nuclear receptor for LTB 4 PPAR␣ and the proinflammatory membrane receptor for LTB 4 BLT2, suggesting that mesothelial cells are responsive to pleural LTB 4 . As expected, mesothelial cells did not express the BLT1 receptor whose expression has been demonstrated to be limited to leukocytes (12) (Fig.…”

Transforming growth factor β1 produced in autocrine/paracrine manner affects the morphology and function of mesothelial cells and promotes peritoneal carcinomatosis

“…Thus, mesothelial cells become hemispherical and exfoliation occurs. Areas of the sub-mesothelial connective tissue are then exposed to peritoneal cavity and this injured peritoneum provides a favorable environment for peritoneal metastasis (8)(9)(10)(11)(12)(13)(14). In this study, we investigated the effects of TGF-ß1 on the morphology and function of human peritoneal mesothelial cells to provide more information on the reciprocal interaction between tumor and mesothelial cells during peritoneal gastric cancer metastasis.…”