Functional characterization of peripheral circulating and liver recruited neutrophils in endotoxic rats.
Neutrophil accumulation in tissue is a hallmark of inflammation and is associated with a variety of pathological conditions. In bacterial infection neutrophils are selectively attracted in large numbers to phagocytose and kill invading microorganisms. However, activated neutrophils can also cause injury to tissues. To investigate functional alterations in liver recruited neutrophils (PMNs), we studied the functional characteristics of circulating blood and liver sequestered PMNs in terms of host defense mechanisms, such as nitric oxide (NO) and superoxide (SO) generation, beta 2 integrin expression, phagocytosis, and eicosanoid profile. Cells were isolated from rats infused with a nonlethal dose (320 micrograms/kg) of E. coli endotoxin (ET) or pyrogen-free saline for 90 min. Liver PMNs produced significantly more NO both in the absence and in the presence of an in vitro endotoxin challenge than did blood PMNs. No significant difference was observed in phorbol myristate acetate-stimulated SO generation. Endotoxin infusion significantly up-regulated the expression of CD11b/c in circulating and even more so in liver PMNs. Phagocytosis was significantly enhanced by in vivo ET treatment in blood PMNs, and liver PMNs showed even greater phagocytic activity than blood PMNs or Kupffer cells. The percent distribution of prostaglandins D2 and E2 of total 14C-eicosanoids was significantly higher and that of thromboxane B2 and 5-, 12-, and 15-HETEs was significantly lower in liver than in blood PMNs. Our study demonstrates several functional differences between liver-recruited and circulating PMNs in an acute endotoxic model. The implications of altered neutrophil function may extend to mechanisms of host defense and hepatotoxicity associated with sepsis and endotoxemia.
Spitzer
J A
JA
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Zhang
P
P
Mayer
A M
AM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D018821:CD18 Antigens; D002478:Cells, Cultured; D004731:Endotoxins / Q000633:toxicity*; D005434:Flow Cytometry; D016023:Integrins / Q000502:physiology; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D010587:Phagocytosis / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D018821:CD18 Antigens; D004731:Endotoxins; D016023:Integrins; D016177:Macrophage-1 Antigen; D010743:Phospholipids; D013481:Superoxides; D016718:Arachidonic Acid; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases