PMID- 1636165
OWN - NLM
STAT- MEDLINE
DCOM- 19920827
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 65
IP  - 6
DP  - 1992 Mar 15
TI  - LPS-induced, but not interferon-gamma-induced procoagulant activity of suspended 
      human macrophages is followed by a refractory state of low procoagulant 
      expression.
PG  - 733-44
AB  - Monocyte-derived macrophages cultured under a variety of conditions were assessed 
      for expression of procoagulant activity (PCA) upon induction by various triggers, 
      using a semiautomated turbidimetric recalcification time assay in a kinetic ELISA 
      reader. Macrophages cultured in a nonadherent (teflon) culture system and seeded 
      in microtiter plates responded with PCA expression to lipopolysaccharide (LPS), 
      to toxic shock-syndrom toxin-1 (TSST-1) and to surface-bound IgG, but not to 
      surface-bound albumin, nor to interferon-gamma (IFN-gamma). In contrast, 
      macrophages stimulated in teflon containers by IFN-gamma showed a strong PCA 
      response peaking around 24 hr after stimulation, but they failed to secrete 
      tumour necrosis factor (TNF). Suspended IFN-gamma-stimulated cells showed a 
      similar response upon 2nd stimulation by LPS or IgG after adherence to microtiter 
      plates as did nonprimed counterparts. In contrast, cells primed in suspension, 
      then cultured in adherence secreted dramatically enhanced amounts of TNF when 
      compared with nonprimed cells. Macrophages stimulated in suspension with LPS 
      showed a PCA response of similar magnitude, which was accompanied by TNF 
      secretion. PCA of both IFN-gamma-primed and LPS-exposed suspension culture cells 
      was largely due to the surface expression of tissue factor, and to a lesser 
      extent of a prothrombinase-like activity, as evidenced by PCA testing with 
      factor-X-deficient plasma. The kinetics of LPS-induced PCA differed from 
      IFN-gamma-induced PCA, in that PCA peaked at 6 hr and fell to insignificant 
      levels after 24 hr. When transferred to microtiter plates at this time, they 
      could be restimulated neither with LPS, nor with surface-adherent IgG nor with 
      IFN-gamma. Evidence was obtained that the failure to express PCA was due to a 
      refractory state of the cells rather than to the generation of cell-bound or 
      secreted inhibitors of coagulation. The loss of PCA expression could be prevented 
      by pre-exposure to IFN-gamma. Thus, PCA expression may be dissociated from other 
      functional and/or activation parameters (e.g. TNF secretion). For the first time, 
      a state in which cells are completely unresponsive to PCA induction has been 
      identified. Should lower LPS concentrations also be found to induce such a 
      refractory state, our results may be of pathophysiological significance.
FAU - Miserez, R
AU  - Miserez R
AD  - Institute of Veterinary Virology, University of Berne, Switzerland.
FAU - Jungi, T W
AU  - Jungi TW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Blood Coagulation Factors/*biosynthesis/metabolism
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/*drug effects
MH  - Nephelometry and Turbidimetry
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 1992/03/15 00:00
MHDA- 1992/03/15 00:01
CRDT- 1992/03/15 00:00
PHST- 1992/03/15 00:00 [pubmed]
PHST- 1992/03/15 00:01 [medline]
PHST- 1992/03/15 00:00 [entrez]
AID - 0049-3848(92)90112-N [pii]
AID - 10.1016/0049-3848(92)90112-n [doi]
PST - ppublish
SO  - Thromb Res. 1992 Mar 15;65(6):733-44. doi: 10.1016/0049-3848(92)90112-n.