PMID- 7692733
OWN - NLM
STAT- MEDLINE
DCOM- 19931105
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 143
IP  - 4
DP  - 1993 Oct
TI  - The production of chemotactic cytokines in an allogeneic response. The role of 
      intercellular adhesion molecule-1 and lymphocyte function-associated antigen-3.
PG  - 1179-88
AB  - The in vitro mixed lymphocyte reaction (MLR) is regarded as a model of 
      responsiveness to allogeneic major histocompatibility complex antigens and has 
      historically been used to elucidate the pathway of T lymphocyte proliferation. In 
      addition, the MLR response may reflect activation pathways relevant in acute 
      allograft rejection. In the present study, we have applied the MLR to examine the 
      role of adhesion molecules intercellular adhesion molecule-1 and lymphocyte 
      function-associated antigen-3 in the induction of tumor necrosis factor-alpha 
      (TNF-alpha) as well as chemotactic cytokines, interleukin-8 (IL-8), monocyte 
      chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 
      alpha). Monoclonal antibodies to the adhesion molecules (5 micrograms/ml) were 
      added to one-way human MLR cultures and supernatants collected at various time 
      points. The monoclonal antibodies to the adhesion molecules significantly 
      suppressed the proliferative response by 50 to 80%. Cytokine production, 
      TNF-alpha (3.2 +/- 0.5 ng/ml), MIP-1 alpha (12.9 +/- 3.3 ng/ml), MCP-1 (18.8 +/- 
      3.4 ng/ml), and IL-8 (57 +/- 18 ng/ml) peaked on day 5 of the assay. The addition 
      of anti-intercellular adhesion molecule-1 to the cultures suppressed TNF-alpha, 
      MIP-1 alpha, MCP-1, and IL-8 production by 68% (1.05 +/- 0.29 ng/ml), 85% (2.0 
      +/- 1.2 ng/ml), 63% (6.8 +/- 2.9 ng/ml), and 47% (30.3 +/- 3.7 ng/ml), 
      respectively. Likewise, the addition of anti-lymphocyte function-associated 
      antigen-3 monoclonal antibody suppressed the cytokines by 78% (0.71 +/- 0.34 
      ng/ml), 66% (4.5 +/- 2.2 ng/ml), 52% (8.8 +/- 2.2 ng/ml), and 73% (15.7 +/- 4.4 
      ng/ml), respectively. Immunohistochemical staining indicated that monocytes were 
      the primary source of the chemokines IL-8, MCP-1, and MIP-1 alpha. The addition 
      of exogenous recombinant TNF-alpha (5 ng/ml) or recombinant IL-2 (5 units/ml) to 
      the anti-intercellular adhesion molecule-1-treated cultures allowed the recovery 
      of the proliferative response as well as restoration of IL-2, TNF-alpha, and 
      IL-8, but not MCP-1 or MIP-1 alpha, indicating that both soluble and adhesion 
      molecule signals are required for the production of the C-C family of chemokines 
      in allogeneic responses. Thus, the events resulting in cellular proliferation and 
      chemokine production were dependent on adhesion molecule interactions.
FAU - Lukacs, N W
AU  - Lukacs NW
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor 
      48109-0360.
FAU - Kunkel, S L
AU  - Kunkel SL
FAU - Burdick, M D
AU  - Burdick MD
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
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  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CD58 Antigens)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukin-8)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Monokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - Antigens, CD/immunology/*physiology
MH  - CD58 Antigens
MH  - Cell Adhesion Molecules/immunology/*physiology
MH  - Cell Division/drug effects
MH  - Chemokine CCL2
MH  - Chemokine CCL4
MH  - Chemotactic Factors/antagonists & inhibitors/*biosynthesis
MH  - Cytokines/antagonists & inhibitors/*biosynthesis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Immunohistochemistry
MH  - Intercellular Adhesion Molecule-1
MH  - Interleukin-2/biosynthesis
MH  - Interleukin-8/antagonists & inhibitors
MH  - *Lymphocyte Culture Test, Mixed
MH  - Macrophage Inflammatory Proteins
MH  - Membrane Glycoproteins/immunology/*physiology
MH  - Monokines/antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/pharmacology
PMC - PMC1887064
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
PMCR- 1994/04/01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
PHST- 1994/04/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Pathol. 1993 Oct;143(4):1179-88.