PMID- 8335925
OWN - NLM
STAT- MEDLINE
DCOM- 19930826
LR  - 20071114
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 151
IP  - 3
DP  - 1993 Aug 1
TI  - Characterization of the production of monocyte chemoattractant protein-1 and IL-8 
      in an allogeneic immune response.
PG  - 1205-13
AB  - Delayed-type hypersensitivity and allograft rejection are dependent upon the 
      generation of Ag-specific T cell immune responses. The mixed lymphocyte reaction 
      is a model of alloantigen-driven immunity and has provided significant insight 
      into the mechanisms of T cell proliferation. Recently, soluble mediators, 
      including TNF-alpha have been shown to be involved in the full expression of this 
      response. In order to elucidate the potential mechanisms of cellular recruitment 
      in the context of either delayed-type hypersensitivity or allograft rejection, we 
      employed a mixed lymphocyte reaction to study the production of chemokines, 
      monocyte chemoattractant protein-1 (MCP-1), and IL-8. Time-course experiments 
      demonstrated that significant levels of MCP-1 and IL-8 were produced in 
      allogeneic cultures as early as day 1, and that this relationship persisted over 
      6 days in culture. Northern blot analysis of chemokine mRNA confirmed the early 
      induction of these genes in the allogeneic response. The levels of MCP-1 and IL-8 
      protein from mixed lymphocyte reaction supernatants as measured by specific ELISA 
      were positively correlated with the proliferative response as measured by [3H]TdR 
      uptake. Although significant MCP-1 and IL-8 were produced during a mixed 
      lymphocyte reaction, these molecules did not participate in the proliferative 
      response, as neutralizing antibodies to either MCP-1 or IL-8 had no effect on 
      proliferation. In order to ascertain the mechanism for the induction of MCP-1 and 
      IL-8 during the mixed lymphocyte reaction, experiments were performed in the 
      presence of neutralizing anti-human TNF antibodies. Neutralization of TNF 
      resulted in significant abrogation of MCP-1 and IL-8 production (75 +/- 5 and 87 
      +/- 2 percent, respectively). Cells isolated from the mixed lymphocyte reaction 
      at day 6, demonstrated that MCP-1 and IL-8 Ag were localized to mononuclear 
      phagocytes. These results demonstrate that potent chemokines, MCP-1 and IL-8, are 
      produced during the evolution of a mixed lymphocyte reaction, and their induction 
      is TNF-dependent.
FAU - Christensen, P J
AU  - Christensen PJ
AD  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 
      48109-0360.
FAU - Rolfe, M W
AU  - Rolfe MW
FAU - Standiford, T J
AU  - Standiford TJ
FAU - Burdick, M D
AU  - Burdick MD
FAU - Toews, G B
AU  - Toews GB
FAU - Strieter, R M
AU  - Strieter RM
LA  - eng
GR  - 1P50HL46487/HL/NHLBI NIH HHS/United States
GR  - HL02401/HL/NHLBI NIH HHS/United States
GR  - HL50057/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Interleukin-8)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
GS  - IL-8
GS  - MCP-1
MH  - Base Sequence
MH  - Chemokine CCL2
MH  - Chemotactic Factors/*physiology
MH  - Gene Expression
MH  - Humans
MH  - *Immunity, Cellular
MH  - Interleukin-8/*physiology
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides/chemistry
MH  - RNA, Messenger/genetics
MH  - Tumor Necrosis Factor-alpha/physiology
EDAT- 1993/08/01 00:00
MHDA- 1993/08/01 00:01
CRDT- 1993/08/01 00:00
PHST- 1993/08/01 00:00 [pubmed]
PHST- 1993/08/01 00:01 [medline]
PHST- 1993/08/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1993 Aug 1;151(3):1205-13.