Oxidative metabolic response and microbicidal activity of human milk macrophages: effect of lipopolysaccharide and muramyl dipeptide.
Mouse macrophages can be primed by exposure in vitro to the bacterial products lipopolysaccharide and muramyl dipeptide (MDP) or in vivo by injection of MDP, so that they produce more of the bactericidal agent superoxide anion (O2-) when stimulated by phagocytosis or by contact with phorbol myristate acetate (PMA). Because little is known about the physiology of human tissue macrophages, we examined release of O2- by milk macrophages obtained from 45 normal women for the ability to undergo priming for greater O2- release. In samples from the same individuals, PMA-stimulated O2- release was similar from colostrum (0 to 3 days postpartum) or from transitional milk (5 to 8 days). Release of O2- by milk macrophages was almost identical to that by blood monocytes from the same women. Milk macrophages phagocytized and killed Candida albicans relatively effectively. Incubation with lipopolysaccharide activated the macrophages in that they were primed for greater PMA-stimulated O2- release. Incubation with the adjuvant MDP or its analog 6-O-(2-tetradecylhexadecanoyl)-MDP did not prime, but incubation with a second analog, 6-O-(stearoyl)-MDP, primed the macrophage for greater O2- release. These results indicated that human tissue macrophages can be primed for greater oxidative response by exposure to bacterial products. Potential exists for the therapeutic use of such immunomodulating agents in the enhancement of host defense.
Cummings
N P
NP
Neifert
M R
MR
Pabst
M J
MJ
Johnston
R B
RB
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D002176:Candida albicans / Q000276:immunology; D003126:Colostrum / Q000276:immunology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008895:Milk, Human / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010101:Oxygen Consumption; D010587:Phagocytosis; D011247:Pregnancy; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008070:Lipopolysaccharides; D013481:Superoxides; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D013755:Tetradecanoylphorbol Acetate