Attenuation of hepatic neutrophil sequestration by anti-CINC antibody in endotoxic rats.
Cytokine-induced neutrophil chemoattractant (CINC) is a member of the chemokine alpha sub-family. It is induced in rats by tumor necrosis factor-alpha (TNF-alpha), interleukin-1, and lipopolysaccharide and is implicated in neutrophil infiltration in response to inflammatory stimuli. We tested the hypothesis that pretreatment with anti-CINC antibody or by cobra venom factor attenuates hepatic neutrophil accumulation induced by a 90 min infusion of Escherichia coli endotoxin. Changes in the expression of CD11b/c and CD18 and in plasma TNF-alpha levels were also investigated. Cultured hepatocytes and Kupffer cells of endotoxic rats produced significantly more CINC than those of saline-infused controls. CINC generation by Kupffer cells was much lower than generation by hepatocytes. Pretreatment with anti-CINC antibody or cobra venom factor significantly reduced hepatic neutrophil sequestration, but did not affect the up-regulation of CD11b/c and CD18 expression on liver-sequestered neutrophils or plasma TNF-alpha levels. We conclude that CINC-mediated hepatic neutrophil accumulation may not be necessarily associated with up-regulation of neutrophil adhesion molecules or elevated circulating TNF-alpha levels. Attenuation of hepatic neutrophil sequestration by anti-CINC antibody is likely based on blocking of the chemotactic activity of CINC and thus diminishing the chemotactic gradient established in the liver.
Zhang
P
P
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Xie
M
M
Zagorski
J
J
Spitzer
J A
JA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000276:immunology* / Q000502:physiology; D004546:Elapid Venoms / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D006133:Growth Substances / Q000276:immunology* / Q000502:physiology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014115:Toxemia / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D018821:CD18 Antigens; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004546:Elapid Venoms; D004731:Endotoxins; D006133:Growth Substances; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; C016310:cobra venom factor