Endotoxin pretreatment inhibits neutrophil proliferation and function.
Gut ischemia/reperfusion (I/R) induces lung injury by a mechanism that involves neutrophils (PMNs). We have previously shown that endotoxin (LPS), when administered after gut I/R, amplifies this lung injury, while treatment with LPS prior to gut I/R prevents lung injury. The purpose of this study was to determine whether LPS pretreatment (Pre Rx) alters the PMN inflammatory component of the gut I/R injury. Specifically, we focused on whether LPS Pre Rx effected (i) PMN stem cell proliferation, (ii) gut I/R-induced PMN priming, and (iii) gut I/R-induced PMN lung sequestration. Bone marrow was harvested from normal and LPS-pretreated (0.5 mg/kg, ip, 3 days prior) rats, and colony forming units--granulocyte/macrophage (CFU-GM) were quantitated using a soft agar culture technique. In another experiment, normal and LPS-pretreated rats were subjected to gut I/R (45 min superior mesenteric artery occlusion/6 hr reperfusion), and blood and lungs were then harvested. The in vivo priming of PMN was assessed by measuring the difference in superoxide production (O2-) with and without the activating stimulus, N-formylmethionyl-leveyl-phenylalanine (fMLP). The quantity of myeloperoxidase (MPO) was used as an index of the number of PMN sequestered in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Koike
K
K
Department of Surgery, Denver General Hospital, Colorado 80204.
Moore
F A
FA
Moore
E E
EE
Trew
C E
CE
Banerjee
A
A
Peterson
V M
VM
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002199:Capillary Permeability; D002455:Cell Division / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D012709:Serum Albumin / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology
D004731:Endotoxins; D012709:Serum Albumin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase