PARC/CCL18 Is a Plasma CC Chemokine with Increased Levels in Childhood Acute Lymphoblastic Leukemia

Abstract

Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissuespecific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1-69) and processed PARC (1-68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients' strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflam-

Up-Regulation of the Chemokine CCL18 by Macrophages Is a Potential Immunomodulatory Pathway in Cutaneous T-Cell Lymphoma

“…25 Expression of CCR3 and its ligands CCL11 and CCL26 has been reported in CTCL. 26,27 In addition to CTCL, CCL18 up-regulation has been described in B-cell leukemia 15 and in gastric and ovarian cancer. 16,28 The expression of CCL18 by CD68 ϩ macrophages in the tumor invasion front was first described in gastric cancer.…”

“…9 -11 CCL18 has been described in T H 2-associated allergic or autoimmune diseases, including atopic dermatitis, 11 bullous pemphigoid, 12 hypersensitivity pneumonitis, 13 and vernal keratoconjunctivitis. 14 Regarding its implication in tumor pathogenesis, elevated serum concentrations of CCL18 have been detected in childhood acute lymphoblastic leukemia, 15 and CCL18 expression was increased in patients with gastric cancer, where it was associated with prolonged overall survival. 16 CCL18 expression can be induced by IL-4.…”

Chemokines synergize in the recruitment of circulating neutrophils into inflamed tissue

“…For example, the inactive hemofiltrate CC chemokine (HCC)-1/CCL14 needs to be proteolytically cleaved at the N terminus to become a potent GPCR agonist [21]. Other plasma CC chemokines such as pulmonary and activation-regulated chemokine (PARC)/CCL18 and regakine-1 and the CXC chemokine platelet factor (PF)-4/CXCL4 seem to be active without post-translational processing [15,16,22]. In this study we show that in both rabbits and mice, regakine-1 alone provoked neutrophil mobilization upon i.v.…”

Serum Level of CC-Chemokine Ligand 18 is Increased in Patients with Non-small-cell Lung Cancer and Correlates with Survival Time in Adenocarcinomas

“…The CC-Chemokine CCL18, previously named ''pulmonary and activation-regulated chemokine'' is strongly expressed in human lungs and less in other lymphatic tissue like lymph nodes or thymus. CCL18, which is constantly present in the serum of healthy subjects, has no counterpart in rodents and its serum level is increased in several benign and malign diseases like lung fibrosis, atopic dermatitis, Gaucher disease, and leukemia [10][11][12][13]. Some authors also demonstrate that the level of CCL18 is elevated in body fluids and serum of patients with ovarian carcinoma [14,15].…”