Comparison of leukotriene B4-induced neutrophil migration through different cellular barriers

Abstract

Migration of neutrophils across epithelial or endothelial barriers in response to chemotactic stimuli occurs in inflammation and host defense. Leukotriene B4 (LTB4) may be synthesized by and certainly induces chemotaxis of neutrophils. To better understand the interaction between LTB4, neutrophils, and endothelium and epithelium, we compared the effects of LTB4 on human peripheral blood neutrophil migration through filters alone and on human umbilical vein endothelial (HUVE) cells and three different epithelial cell types, Madin-Darby canine kidney (MDCK) cells, human colon carcinoma (T84) cells, and rat type II alveolar cells, cultured on these filters. Significant LTB4-stimulated neutrophil migration occurred at the lowest (1 nM) dose and in the shortest period of time (15 min) across endothelial cells vs. all three epithelial cell types, and interestingly, vs. filters alone. Dose-response experiments (1-100 nM) indicated that at equimolar LTB4 concentrations neutrophil migration across endothelium was two- to threefold greater than that observed across filters alone and the three epithelial barriers. At higher LTB4 concentrations (100 nM), the degree of neutrophil migration through the three epithelial barriers was equivalent to that observed for filters alone. Overall, the data indicate that the various cellular barriers play an active role in inflammatory processes by regulating the transmigration of neutrophils in response to certain inflammatory chemotactic stimuli.

The Microcirculation and Inflammation: Site of Action for Glucocorticoids

“…During this phase, the leukocyte can be activated to become firmly adherent. Examples of leukocyte activators are chemoattractants including leukotriene B 4 or complement factor C5a (25,28), chemokines including interleukin-8 or monocyte chemoattractant protein 1 (119,120), and nonclassical activators such as substance P (46). The step of leukocyte firm adherence is mediated by integrin activation with consequent increased avidity for the counterligands (examples are the ␤ 2 -integrins that bind to intercellular adhesion molecule-1 (ICAM-1) and intercellular adhesion molecule-2 (ICAM-2), and the ␤ 1 -integrins that bind to vascular cell adhesion molecule-1 (VCAM-1).…”

Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri.

“…Together with the canine epithelial cell line MDCK ( 19), this cell line has been used to assess transepithelial movement of neutrophils in response to chemotactic gradients achieved by compounds such as the bacteria-derived N-formylated peptides (20). This event is crucial in host defense (21 ) and has been modeled by several authors (22)(23)(24)(25)(26), using different chemotactic agents to induce transmigration of neutrophils across cultured epithelial monolayers. PMN transmigration requires specific adhesive interaction with epithelial cells.…”

Promoting detachment of neutrophils adherent to murine postcapillary venules to control inflammation: Effect of lipocortin 1

“…During this phase the neutrophil can be activated, causing it to firmly adhere. Examples of such activators include chemoattractants such as leukotriene B 4 or complement factor C5a (3,4), chemokines such as interleukin-8 (IL-8) or monocyte chemoattractant protein 1 (5,6), members of the S100 family such as CP-10 and the complex MRP8͞14 (7,8), and, finally, nonclassical activators such as substance P (9). Firm adhesion is associated with integrin activation and increased avidity for the counter-ligands (10).…”