PMID- 1647275
OWN - NLM
STAT- MEDLINE
DCOM- 19910801
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 69
IP  - 1
DP  - 1991 Jul
TI  - Priming by platelet-activating factor of endotoxin-induced lung injury and 
      cardiovascular shock.
PG  - 12-25
AB  - Platelet-activating factor (PAF) is a glycerophospholipid known for its unusual 
      potent vasoactive and proinflammatory activities. The present study examined 
      whether PAF might serve as a priming factor in endotoxin-induced tumor necrosis 
      factor-alpha (TNF alpha) synthesis, cardiovascular shock, and lung injury in 
      anesthetized rats. Intravenous infusion of PAF (1 pmol/kg/min for 60 minutes, n = 
      5) alone or endotoxin (0.1 micrograms/kg i.v. bolus, n = 5) failed to alter blood 
      pressure, serum TNF alpha and thromboxane B2, platelet and leukocyte count, and 
      hematocrit, nor was lung histology, myeloperoxidase activity, and water content 
      changed. In contrast, the combined administration of PAF and endotoxin markedly 
      elevated serum TNF alpha (1,359 +/- 362 pg/ml, n = 5, p less than 0.01) and 
      thromboxane B2 (43 +/- 5 pg/100 microliters, n = 8, p less than 0.01) along with 
      hypotension, hemoconcentration, leukopenia, and thrombocytopenia. Most notably, 
      the combined regimen caused neutrophil aggregation, adhesion, and accumulation 
      into the lung parenchyma along with platelet-fibrin deposits in postcapillary 
      venules, pulmonary edema, and increased lung myeloperoxidase activity. The role 
      of PAF in this process was confirmed by 1) the prevention of the priming effect 
      by pretreatment with the PAF antagonist BN 50739 (n = 5), and 2) the failure of 
      lyso-PAF, the cardinal nonactive PAF-metabolite, to prime for endotoxin-induced 
      production of TNF alpha (n = 4). These data suggest that PAF could serve as a key 
      mediator in priming for endotoxin-induced tissue injury, especially the typical 
      pulmonary pathophysiology of adult respiratory distress syndrome, a severe 
      pathological outcome of septic shock, burns, and multiple organ injury.
FAU - Rabinovici, R
AU  - Rabinovici R
AD  - Department of Surgery, Jefferson Medical College, Philadelphia, Pa 19107.
FAU - Esser, K M
AU  - Esser KM
FAU - Lysko, P G
AU  - Lysko PG
FAU - Yue, T L
AU  - Yue TL
FAU - Griswold, D E
AU  - Griswold DE
FAU - Hillegass, L M
AU  - Hillegass LM
FAU - Bugelski, P J
AU  - Bugelski PJ
FAU - Hallenbeck, J M
AU  - Hallenbeck JM
FAU - Feuerstein, G
AU  - Feuerstein G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Endotoxins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 54397-85-2 (Thromboxane B2)
RN  - EC 1.11.1.7 (Peroxidase)
SB  - IM
MH  - Animals
MH  - Body Water/metabolism
MH  - Cardiovascular Diseases/blood/*chemically induced/physiopathology
MH  - Drug Synergism
MH  - *Endotoxins
MH  - *Escherichia coli
MH  - Hemodynamics/drug effects
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/enzymology/pathology
MH  - Lung Diseases/blood/*chemically induced/physiopathology
MH  - Male
MH  - Microscopy, Electron, Scanning
MH  - Organ Size
MH  - Peroxidase/metabolism
MH  - *Platelet Activating Factor/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Thromboxane B2/blood
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1991/07/01 00:00
MHDA- 1991/07/01 00:01
CRDT- 1991/07/01 00:00
PHST- 1991/07/01 00:00 [pubmed]
PHST- 1991/07/01 00:01 [medline]
PHST- 1991/07/01 00:00 [entrez]
AID - 10.1161/01.res.69.1.12 [doi]
PST - ppublish
SO  - Circ Res. 1991 Jul;69(1):12-25. doi: 10.1161/01.res.69.1.12.