The kinetics of messenger RNA (mRNA) and protein levels pounds. 1 Thus, neutrophils were thought to be relevant only of cytokine-induced neutrophil chemoattractant (CINC) in rat to the efferent limb of the immune response. However, it has hepatic allografts during acute rejection were investigated. been shown that neutrophils contribute significantly to the Infiltrating cells were identified by double immunostaining afferent or inductive limb of the immune response by moduwith anti-CINC and anti-macrophage monoclonal antibodies, lating both cellular and humoral immunity, particularly via ED1 and ED2. The serum CINC concentration in untreated the synthesis and release of immunoregulatory cytokines, hepatic allograft recipients increased significantly at a such as interleukin-1 (IL-1), tumor necrosis factor a (TNFconstant rate over time after transplantation. No significant a), and interleukin-6 (IL-6). 2 Hence, neutrophils modulate increases in serum CINC concentrations were observed in both T-and B-cell activities in the evolution of an immune hepatic isografts or allografts treated with the immunosupresponse. pressant FK506. The number of neutrophils in untreated he-Neutrophils have been implicated as mediators of tissue patic allografts increased significantly at a constant rate. Condamage in a variety of diseases. 3,4 However, the role of neuversely, neutrophil accumulation in isografts or allografts trophils in organ allograft rejection is not well understood. treated with FK506 was much less than in untreated hepati-Tissue injury may occur in the process of organ transplantacallografts. Immunostaining revealed that in the portal areas, tion secondary to ischemia/reperfusion, rejection, and drug mononuclear cells infiltrating untreated allograft liver were toxicity. Neutrophils may contribute to such injuries. In fact, mainly positive for CINC and that CINC / cells represented ischemia/reperfusion generates mediators that include free a subpopulation (Ç25%) of the ED1 / cells. On the other radicals, and causes protease activation. In addition, many hand, in the sinusoidal areas CINC / cells were scattered and of the pathological changes noted after ischemia/reperfusion mainly positive for ED2. Levels of CINC mRNA in liver tisinjury are thought to be induced by infiltrating neutrophils. sues taken from untreated hepatic allografts increased after Jaeschke et al. 5 and Poggetti et al. 6 have shown the importransplantation, peaked on day 5, and decreased thereafter. tance of neutrophils in the development of schemia/reperfu-Hepatic allografts treated with FK506 or isografts showed sion injury. much lower levels of CINC mRNA than untreated allografts.
Accumulation of neutrophils is mediated by local chemo-Allogeneic mixed lymphocyte reactions induced CINC protactic agents. Increased production and release of these subduction. The cellular source of CINC was mononuclear cells. stances regulate neutrophil migration from the vascular CINC production in mixed lymphocyte reactions was inhibcompartment to the tissues. A tissue-derived neutrophil-actiited in the presence of anti-tumor necrosis factor a (TNF-a) vating peptide (NAP-1), which is identical to interleukin- antibody. These results suggest that enhanced expression of 8 (IL-8), has been cloned. 7 The effects of IL-8 on human CINC mRNA and prominent accumulation of neutrophils in neutrophil functions include enhanced chemotaxis, enzyme the liver grafts are characteristic features of the immune rerelease, expression of surface adhesion molecules, and inducsponse during acute rejection. (HEPATOLOGY 1997;26:1546tion of the respiratory burst. 7 1552.)
No substance homologous to IL-8 has been identified in the rat. However, potent neutrophil chemotactic activity has Neutrophil has long been regarded merely as a terminally been detected in rat inflammatory exudate induced by lipodifferentiated cell capable of protein synthesis, and fulfilling polysaccharide, TNF-a, or IL-1. [8][9][10][11] Cytokine-induced neuonly a passive effector role in inflammation via phagocytosis trophil chemoattractant (CINC) is an 8-kd polypeptide origiand the release of preformed enzymes and cytotoxic comnally identified in conditioned media from IL-1 b-stimulated rat glomerular epithelial cells and subsequently purified from NRK52E rat epithelioid cells. 8 CINC consists of 72 amino acids and has homology to human peptides with gro/mela-Abbreviations: IL-1, interleukin-1; TNF-a, tumor necrosis factor a; IL-6, interleunoma growth stimulatory activities, indicating that rat CINC kin-6; IL-8, interleukin-8; CINC, cytokine-induced neutrophil chemoattractant; MLR, mixed lymphocyte reaction; mRNA, messenger RNA; PBMC, peripheral blood mononu-belongs to the IL-8 superfamily. 9,10 Thus, the regulation of clear cell.