Human alveolar macrophage gene expression of interleukin-8 by tumor necrosis factor-alpha, lipopolysaccharide, and interleukin-1 beta.
The alveolar macrophage (AMO) in its pivotal position for pulmonary host defense may play a prominent role in the orchestration of polymorphonuclear leukocyte (PMN) diapedesis. We demonstrate that the human AMO may participate in these inflammatory events through the production of a novel neutrophil chemotactic factor, interleukin-8 (IL-8). The induction of AMO-derived IL-8 by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interleukin-1 (IL-1 beta) was shown to be both dose and time dependent. Maximal IL-8 gene expression, as assessed by Northern blot analyses, was achieved with 20 ng/ml and 1 microgram/ml, respectively, for each of the cytokines and LPS. A kinetic study of TNF-, IL-1 beta-, and LPS-treated AMOs showed significant steady-state IL-8 mRNA accumulation post-stimulation at 1 h, peaking by 8 h, with a decline over the next 16 h. Immunohistochemical staining using rabbit anti-human IL-8 antibody demonstrated significant immunolocalization of cell-associated IL-8 antigen at 4 h, with persistence over the next 20 h. Chemotactic bioactivity peaked by 8 h, with continued production over the next 16 h. Chemotactic bioactivity from AMO-conditioned media was inhibited by IL-8 antiserum by 2, 31, 44, and 47%, respectively, for unstimulated control, LPS-, IL-1 beta-, and TNF-treated cells. Preimmune serum had no effect on chemotactic activity. These data support the central role of the AMO in the elicitation of PMNs into the lung via the production of IL-8.
Strieter
R M
RM
Department of Pathology, University of Michigan Medical School, Ann Arbor.
Chensue
S W
SW
Basha
M A
MA
Standiford
T J
TJ
Lynch
J P
JP
Baggiolini
M
M
Kunkel
S L
SL
D002630:Chemotactic Factors / Q000235:genetics* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8; D007378:Interleukins / Q000235:genetics* / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002630:Chemotactic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha