Recombinant interferon-gamma primes alveolar macrophages cultured in vitro for the release of leukotriene B4 in response to IgG stimulation.
The capacity of interferon-gamma to regulate the generation and release of leukotriene B4 (LTB4) from human alveolar macrophages of normal nonsmoking individuals was evaluated. When alveolar macrophages were incubated for 60 min with heat aggregated IgG (HAIgG), they generated and released 5.7 +/- 1.7 ng of LT B4 per 10(6) cells compared to 1.9 +/- 0.4 ng from cells incubated with buffer alone, P = 0.02. When alveolar macrophages were preincubated with interferon-gamma for 24 h before activation for 60 min with heat-aggregated IgG, the soluble IgG aggregates became a significantly more effective stimulus for LTB4 release, 17.0 +/- 3.9 ng/10(6) cells, P = 0.001, compared to cells incubated in the absence of interferon-gamma and challenged with HAIgG. Interferon-gamma did not alter the response to A23187. This effect of interferon-gamma was both time and dose dependent; it also was specific since neither interferon-alpha nor interferon-beta had a regulatory effect on the release of LTB4 from cells in response to challenge with HAIgG. Preincubation of the alveolar macrophages with interferon-gamma augmented the density of IgG1 receptors by 81.5 +/- 17.3%; neither interferon-alpha nor interferon-beta effected this parameter. Furthermore, monomeric IgG1 blocked HAIgG induced LTB4 release from alveolar macrophages primed with interferon-gamma. Therefore, at least one of the mechanisms by which interferon-gamma primes alveolar macrophages for the production and release of LTB4 in response to stimulation by aggregates of IgG is that of increasing the number of receptors for this stimulus.
Rankin
J A
JA
Research Service, West Haven Veterans Hospital, Connecticut 06516.
Schrader
C E
CE
Smith
S M
SM
Lewis
R A
RA
D000943:Antigens, Differentiation / Q000378:metabolism; D000001:Calcimycin; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003571:Cytochalasin B; D004731:Endotoxins; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D011650:Pulmonary Alveoli; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG; D011994:Recombinant Proteins; D012397:Rosette Formation
D000943:Antigens, Differentiation; D004731:Endotoxins; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007975:Leukotriene B4; D000001:Calcimycin; D003571:Cytochalasin B; D007371:Interferon-gamma