Alveolar macrophages differ from blood monocytes in human IL-1 beta release. Quantitation by enzyme-linked immunoassay.
Fresh human alveolar macrophages and blood monocytes were stimulated with LPS and assessed for their ability to produce and release antigenic IL-1 beta. Using a sensitive and specific ELISA for IL-1 beta, monocytes released 13.3 +/- 3.1 ng/10(6) cells compared to 3.5 +/- 0.8 ng/10(6) cells for alveolar macrophages (p less than 0.01). To investigate the reason for this difference in IL-1 beta release, monocytes were compared to alveolar macrophages for total IL-1 beta production (i.e., the amount released plus that detected in the lysates). Monocytes produced a total of 19.0 +/- 3.2 ng/10(6) cells whereas alveolar macrophages produced 24.8 +/- 5.6 ng/10(6) cells (p = 0.37). The relative increase in alveolar macrophage intracellular IL-1 beta was confirmed by Western blot analysis of cell lysates. Thus, the limitation in IL-1 release from alveolar macrophages appears to be due to a decrease in the processing and release of the IL-1 beta precursor. In addition, TNF production studies demonstrated that the limitation in IL-1 release was not a generalized defect. In contrast to the IL-1 beta data, when TNF was measured from monocytes and macrophages, monocytes released only 14.6 +/- 3.4 ng/10(6), whereas macrophages released 101 +/- 30 ng/10(6) (p less than 0.02). In this same context, when fresh monocytes were allowed to mature in vitro they took on monokine production characteristics similar to alveolar macrophages. In vitro matured monocytes had a greater than 20-fold decrease in their ability to release IL-1 beta and a 6- to 8-fold increase in their ability to release TNF. Taken together, these studies suggest that IL-1 beta release is limited in mature mononuclear phagocytes as compared to fresh blood monocytes, and furthermore, that IL-1 beta regulation differs significantly from that of TNF-alpha.
Wewers
M D
MD
Department of Medicine, Ohio State University, Columbus 43210.
Herzyk
D J
DJ
D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000592:standards; D008262:Macrophage Activation; D008264:Macrophages / Q000032:analysis* / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000032:analysis* / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D004731:Endotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha