Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan

John A. Rankin, Ilona Sylvester, Sharon Smith, T. Yoshimura, Edward J. Leonard

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The capacity of lipopolysaccharide (LPS), zymosan, arid calcium ionophore A23187 to induce neutrophil chemotactic activity (NCA), leukotriene B4 (LTB4), and neutrophil attractant/activation protein (NAP-1) release from human alveolar macrophages (AM) retrieved from normal nonsmokers was evaluated. LPS induced a dose-dependent release Of LTB4 that began by 1 h, 4.0±3.2 ng/106 viable AM; peaked at 3 h, 24.7±13.5 ng/106 viable AM; and decreased by 24 h, 1.2±1.0 ng/106 viable AM (n = 8). Quantities of LTB4 in cell-free supernatants of AM stimulated with LPS were determined by reverse-phase high-performance liquid chromatography and corresponded well with results obtained by radioimmunoassay. By contrast, NAP-1 release began ∼ 3-5 h after stimulation of AM with LPS, 197±192 ng/ml, and peaked at 24 h, 790±124 ng/ml. Release of NAP-1 was stimulus specific because A23187 evoked the release of LTB4 but not NAP-1, whereas LPS and zymosan induced the release of both LTB4 and NAP-1. The appearance of neutrophil chemotactic activity in supernatants of AM challenged with LPS for 3 h could be explained completely by the quantities of LTB4 present. After stimulation with LPS or zymosan for 24 h, AM had metabolized almost all generated LTB4. Preincubation of AM with nordihydroguiaretic acid (10-4 M) completely abolished the appearance of NCA, LTB4, and NAP-1 in supernatants of AM challenged with LPS. Therefore, LPS and zymosan particles were potent stimuli of the sequential release of LTB4 and NAP-I from AM.

Original languageEnglish
Pages (from-to)1556-1564
Number of pages9
JournalJournal of Clinical Investigation
Issue number5
Publication statusPublished - Nov 1990
Externally publishedYes



  • Alveolar macrophages
  • Interleukin 8
  • Leukotriene B
  • Lipopolysaccharide
  • Neutrophil attractant/activation protein
  • Zymosan

ASJC Scopus subject areas

  • Medicine(all)

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