-transparent.png){kind=logo}
Once infected by obligate intracellular pathogens, monocytes/macrophages release cytokines that activate natural killer (NK) cells. NK cells in turn produce and secrete monocyte/macrophage activating factors such as interferongamma (IFN-gamma), which are important in the early control of these infections. Here we demonstrate that human NK cells are potent producers of another monocyte/macrophage-activating factor, macrophage inflammatory protein-1 alpha (MIP-1 alpha). Fresh NK cells produce negligible amounts of MIP-1 alpha after stimulation with the monocyte-derived cytokines IL-12, TNF-alpha, IL-1 beta, or IL-10, while stimulation with IL-15 alone results in modest MIP-1 alpha production. Abundant NK cell production MIP-1 alpha is seen after costimulation with IL-12 and IL-15, and is dose-dependent. Combinations of IL-12, with TNF-alpha, IL-1 beta, or IL-10 are substantially less effective inducers of MIP-1 alpha production by NK cells. NK cell MIP-1 alpha mRNA transcripts were detectable within 1 h after costimulation with IL-12 plus IL-15 and steadily increased over 24 h, with a concomitant increase in protein production detectable at 12 h. Resting NK cells constitutively express mRNA transcript for a MIP-1 alpha receptor, and costimulation with IL-12 and IL-15 upregulates its level of expression. Equilibrium binding studies with radioiodinated MIP-1 alpha were consistent with the induction of a single class of high affinity MIP-1 alpha receptors on NK cells costimulated with IL-12 and IL-15. Addition of exogenous MIP-1 alpha to resting NK cells did not enhance cytokine production, but did increase NK cytotoxic activity. The requirement for IL-15 as a critical cofactor for NK cell production MIP-1 alpha suggests a potentially unique role for this monocyte-derived cytokine in combination with IL-12. As MIP-1 alpha is known to potentiate the action of IFN-gamma on monocytes and to suppress human immunodeficiency virus replication, the NK cell's production of MIP-1 alpha may be important during the innate immune response to infection.
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
January 2018,
Frontiers in immunology,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
May 1997,
The Journal of experimental medicine,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
October 1995,
American journal of reproductive immunology (New York, N.Y. : 1989),
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
November 2007,
Journal of leukocyte biology,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
May 1991,
The Journal of biological chemistry,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
January 1995,
Clinical immunology and immunopathology,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
October 1993,
The Journal of clinical investigation,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
June 1999,
Journal of immunology (Baltimore, Md. : 1950),
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
July 1993,
The Journal of experimental medicine,
E M Bluman, and
K J Bartynski, and
B R Avalos, and
M A Caligiuri
April 1994,
The American journal of pathology,
