Interleukin-8 mediates interleukin-1 alpha-induced neutrophil transcellular migration.
Interleukin-1 alpha (IL-1 alpha) is a cytokine with a myriad of potent proinflammatory effects. Neutrophils are important immune effector cells in allergic and inflammatory lung diseases. We examined the effects of IL-1 alpha on human neutrophil migration across naked filters and human umbilical vein endothelial (HUVE) cell and type II-like pulmonary epithelial cell (A549) monolayers cultured on these filters. IL-1 alpha from 10(-13) to 10(-9) M induced dose-dependent neutrophil migration through both HUVE and A549 cellular monolayers but not through naked filters. Neutrophil migration was consistently greater through A549 monolayers compared with HUVE monolayers. IL-1 alpha-induced neutrophil migration was also time dependent, and the kinetics of neutrophil migration through HUVE and A549 monolayers were similar. Significant migration through either monolayer was not observed until 2 h, and maximal migration occurred at 3 h through A549 and 5 h though HUVE cellular monolayers. Supernatants of IL-1 alpha (10(-11) M)-stimulated HUVE and A549 monolayers induced significantly more migration of neutrophils across naked filters than 10(-11) M IL-1 alpha itself, suggesting the release of soluble secondary chemotactic factor(s). Pretreatment of HUVE and A549 monolayers with actinomycin D inhibited both IL-1 alpha-induced production of soluble chemotactic factor(s) and transcellular migration by > 90%. Supernatants from IL-1 alpha-treated HUVE and A549 cells contained significant concentrations of interleukin 8 (IL-8), and coincubation of these supernatants with anti-IL-8 inhibited approximately 50% of supernatant-induced chemotaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
Bittleman
D B
DB
Department of Internal Medicine, VA Medical Center, Iowa City, Iowa, USA.
Casale
T B
TB
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*
D007375:Interleukin-1; D016209:Interleukin-8; D003609:Dactinomycin