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Macrophage function in response to PGE 2 , L‐arginine deprivation, and activation by colony‐stimulating factors is dependent on hematopoietic stimulus
Author(s) -
Rutherford Mark S.,
Schook Lawrence B.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.2.228
Subject(s) - tumor necrosis factor alpha , biology , lipopolysaccharide , granulocyte macrophage colony stimulating factor , secretion , endocrinology , medicine , haematopoiesis , macrophage colony stimulating factor , cytokine , macrophage , granulocyte , immunology , in vitro , microbiology and biotechnology , biochemistry , stem cell
Different macrophage preparations were compared for functional capacity in conditions of high prostaglandin E 2 (PGE 2 ) or low l‐arginine concentrations. Macrophages derived in vitro from bone marrow progenitor cells (bone marrow‐derived macrophages, BMDMs) using colony‐stimulating factor 1 (CSF‐1) as the myelopoietic stimulus displayed a greater sensitivity to PGE 2 ‐induced suppression of tumor necrosis factor a (TNF‐α) secretion than did macrophages derived using granulocyte‐macrophage colony‐stimulating factor (GM‐GSF). Neither BMDM population was inhibited by PGE 2 for the direct cytolysis of L929 cells (TNF‐α sensitive), and only GM‐CSF–derived macrophages showed decreased killing of TNF‐α–resistant K562 targets. Exogenous cAMP inhibited TNF‐α secretion, but not nitrite secretion, by both BMDM populations. GM‐GSF–derived macrophages accumulated less cAMP following PGE 2 treatment than did CSF‐1–derived macrophages. Removing l‐arginine from the medium did not inhibit cytotoxicity or PGE 2 secretion, but the listeriacidal activity specific to interferon‐γ plus lipopolysaccharide (LPS)‐activated GM‐CSF–derived macrophages was blocked by removal of l‐arginine. Treatment with CSF‐1 or GM‐CSF alone did not activate the macrophages, but GM‐CSF efficiently primed both BMDM populations for augmented TNF‐α secretion in response to secondary stimulation using LPS. However, GM‐CSF augmented the LPS‐induced production of nitrite and PGE 2 by CSF‐1–derived macrophages only. These results demonstrate the potential for differential macrophage function within inflammatory sites based on the hematopoietic stimulus under which the macrophage is derived and the specific conditions present in the lesion.