Demonstration by in situ hybridization of dissimilar IL-1 beta gene expression in human alveolar macrophages and blood monocytes in response to lipopolysaccharide.
IL-1 beta is the major form of IL-1 produced by mononuclear phagocytes. To evaluate the possible mechanisms underlying the observation that mature populations of human mononuclear phagocytes as alveolar macrophages are relatively poor IL-1 producers compared with blood monocytes, the expression of the IL-1 beta gene mRNA transcripts was evaluated in LPS-stimulated normal autologous blood monocytes and alveolar macrophages by using a IL-1 beta cDNA probe. Although Northern analysis demonstrated that stimulated monocytes and alveolar macrophages both express 1.8-kb IL-1 beta mRNA transcripts, cytoplasmic dot blot analysis showed that the total IL-1 beta mRNA content in alveolar macrophages was only 38 +/- 5% of that in blood monocytes. In situ hybridization with antisense and sense IL-1 beta RNA probes demonstrated that whereas most of stimulated blood monocytes contained IL-1 beta mRNA transcripts, a significant proportion of autologous alveolar macrophages stimulated in an identical fashion did not express the IL-1 beta gene. Within 4 h after LPS stimulation, IL-1 beta mRNA transcripts were detected in 81 +/- 6% monocytes, whereas only 16 +/- 9% of alveolar macrophages were positive, and by 18 h this had increased only to 43 +/- 15%. Quantification of the size distribution of the IL-1 beta mRNA expressing mononuclear phagocytes demonstrated that, among the population of alveolar macrophages, the cells expressing this gene were not confined to those that were "monocyte-like." These observations demonstrate that there is a heterogeneity among population of mononuclear phagocytes in their ability to express the gene for IL-1 beta, which could explain the differences observed in IL-1 production.
Bernaudin
J F
JF
Pathology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Yamauchi
K
K
Wewers
M D
MD
Tocci
M J
MJ
Ferrans
V J
VJ
Crystal
R G
RG
D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011650:Pulmonary Alveoli / Q000166:cytology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000302:isolation & purification
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger