Activation of rat and human alveolar macrophage intracellular microbicidal activity by a preformed LGL cytokine.

Abstract

An alveolar macrophage-activating factor was released from Percoll fractionated large granular lymphocytes (LGL) within minutes of contact with either the natural killer (NK)-sensitive K562 tumor or heat-killed Staphylococcus aureus. The factor enhanced the intracellular killing of S. aureus without altering the rate of phagocytosis. Factor release was blocked by treatment of LGL with monensin, a carboxylic ionophore that inhibits vesicular traffic, but was unaffected by actinomycin D and cycloheximide pretreatment, suggesting that the cytokine was performed. The cell producing the factor was found only in Percoll fractions containing high concentrations of lytic NK cells and LGL, and the phenotypes of the LGL were HNK-1+ and E rosette-. The macrophage activating factor was a small protein of 10,000 to 20,000 daltons, as determined by gel fractionation, and was sensitive to proteolytic enzymes and heat and pH labile. Active supernatants were devoid of antiviral (interferon; IFN) or interleukin 2 (IL 2) activity, and IFN-beta, IFN-gamma, IL 2, and interleukin 1 were unable to activate staphylococcidal activity, suggesting that the LGL macrophage activating factor was distinguishable from these cytokines.