PMID- 8675682
OWN - NLM
STAT- MEDLINE
DCOM- 19960812
LR  - 20210102
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 97
IP  - 12
DP  - 1996 Jun 15
TI  - Human natural killer cells produce abundant macrophage inflammatory protein-1 
      alpha in response to monocyte-derived cytokines.
PG  - 2722-7
AB  - 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.
FAU - Bluman, E M
AU  - Bluman EM
AD  - Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo, New 
      York 14263, USA.
FAU - Bartynski, K J
AU  - Bartynski KJ
FAU - Avalos, B R
AU  - Avalos BR
FAU - Caligiuri, M A
AU  - Caligiuri MA
LA  - eng
GR  - CA68456-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Chemokine CCL4)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-15)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukins)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Monokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Cell Line
MH  - Chemokine CCL4
MH  - Cytokines/*pharmacology
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-15
MH  - Interleukin-2/pharmacology
MH  - Interleukins/pharmacology
MH  - Killer Cells, Natural/*drug effects/metabolism
MH  - Macrophage Inflammatory Proteins
MH  - Monokines/*biosynthesis/genetics
MH  - RNA, Messenger/analysis
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC507364
EDAT- 1996/06/15 00:00
MHDA- 1996/06/15 00:01
PMCR- 1996/06/15
CRDT- 1996/06/15 00:00
PHST- 1996/06/15 00:00 [pubmed]
PHST- 1996/06/15 00:01 [medline]
PHST- 1996/06/15 00:00 [entrez]
PHST- 1996/06/15 00:00 [pmc-release]
AID - 10.1172/JCI118726 [doi]
PST - ppublish
SO  - J Clin Invest. 1996 Jun 15;97(12):2722-7. doi: 10.1172/JCI118726.