Endotoxemia and neutrophil activation in vivo.
There is a growing body of data to suggest that marginated granulocytes mediate much of the pulmonary damage observed during endotoxemia. The mechanism(s) by which endotoxemia initiates neutrophil margination and cytotoxicity remain either controversial or unknown. The objectives of this study were 1) to determine the temporal relationship between endotoxin-induced decreases in mean arterial pressure and circulating neutrophils, 2) to monitor neutrophil activation in vivo by measuring myeloperoxidase (MPO) activity in the plasma and lymph, and 3) to assess the interaction between endotoxin and complement in activation of neutrophilic oxidative metabolism in vitro. We found that a bolus injection of endotoxin causes a concurrent decrease in both mean arterial pressure and circulating neutrophils at 2 min postinfusion. Blood pressure recovered to approximately 70% of control values by 180 min, whereas circulating neutrophils remain depressed at 20% of control values for the entire experimental period. Using MPO as a marker for neutrophil activation, we found that infusion of endotoxin produces a dramatic increase in plasma and lymph MPO activity, suggesting activation of neutrophilic metabolism in vivo. In vitro data showed that both endotoxin and plasma were required for optimal neutrophilic degranulation and superoxide formation. We conclude that 1) the appearance of MPO in the plasma (or lymph) may be a useful neutrophil marker for neutrophil activation in vivo and may prove useful in following the course of neutrophil-mediated tissue injury during endotoxemia, and 2) endotoxin-activated complement (C5a) activates neutrophils to produce cytotoxic oxidants.
Grisham
M B
MB
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130-3932.
Everse
J
J
Janssen
H F
HF
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003182:Complement C5 / Q000378:metabolism; D015936:Complement C5a; D003571:Cytochalasin B / Q000378:metabolism; D004285:Dogs; D004731:Endotoxins / Q000097:blood*; D005260:Female; D007958:Leukocyte Count; D008297:Male; D009503:Neutropenia / Q000209:etiology; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D018805:Sepsis / Q000097:blood* / Q000150:complications; D013481:Superoxides / Q000097:blood
D003182:Complement C5; D004731:Endotoxins; D013481:Superoxides; D003571:Cytochalasin B; D015936:Complement C5a; D009195:Peroxidase