Disease relevance of Ccl5

• Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats [1].
• Although CCL5/RANTES expression was observed during the entire course of the disease, anti-RANTES treatment had no effect on clinical disease progression [2].
• The initial expression of the chemokines closely correlated with the appearance of inflammatory cells in the injured CNS, suggesting that RANTES and MIP-1 beta may play a role in the inflammatory events of traumatic brain injury [3].
• Using a stab wound model for mechanical injury, we studied the expression of two other beta chemokines: RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) and MIP-1 beta (macrophage inflammatory protein-1 beta) in the rat brain [3].
• Colonic RANTES mRNA expression was also significantly elevated during the chronic phase of colitis [4].

High impact information on Ccl5

• In contrast to the consequences of MCP-1 binding, we were unable to demonstrate ligand-dependent calcium fluxes on binding of Rantes to human monocytes or THP-1 cells [5].
• Receptor affinity for Rantes is enhanced on preparation of isolated membranes with a 12-fold decrease in receptor Kd [5].
• These findings were associated with a reduction in eotaxin mRNA and an increase in mRNA for the T-cell chemokines macrophage inflammatory protein-2 (MIP-2), MIP-1beta, and RANTES [6].
• Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1 [7].
• RANTES (regulated upon activation, normal T-cell expressed and secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was maximally expressed at 6 weeks [7].

Chemical compound and disease context of Ccl5

• However, ethanol alone primed isolated Kupffer cells for enhanced RANTES mRNA and protein release in the presence or absence of HIV-1 gp120 [8].
• These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway [9].

Biological context of Ccl5

• CCR3, another RANTES/CCL5 receptor, was constitutively high on macrophages in vivo and in vitro, with down-regulation during AIA [10].
• The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes [11].
• These data show that chemotaxis for GILs is upregulated locally during lung allograft rejection, and that MCP-1 and RANTES contribute to GIL recruitment during the rejection response [12].
• The lymphocyte chemoattractant RANTES had delayed kinetics, with a rise at Day 3, a peak at Day 4, and a gradual decline [13].
• RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor [14].

Anatomical context of Ccl5

• RESULTS: CCR1, a receptor for macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 and RANTES/CCL5, exhibited high constitutive expression on macrophages in AIA [10].
• Monocyte chemoattractant protein-1 and RANTES are chemotactic for graft infiltrating lymphocytes during acute lung allograft rejection [12].
• Immunohistochemistry showed that alveolar macrophages (AMs) were the major source of MCP-1 and that other lung cells, including AMs, were the source of RANTES [12].
• Double-labeling studies showed that MIP-1 beta, but not RANTES, was expressed by reactive astrocytes near the lesion site [3].
• Electron microscopy (x13,800) studies of skin injection sites revealed that RANTES was chemoattractant for mast cells [15].

Associations of Ccl5 with chemical compounds

• RESULTS: Indomethacin, to a lesser degree the selective COX-2 inhibitors, enhanced glomerular MCP-1 and RANTES mRNA levels [16].
• Since PGD2 is formed by mast cells on cell activation, we also studied the effect of RANTES and MCP-1 on PGD2 production in inflamed tissue in vivo [15].
• Here, we report that intradermal injection of RANTES 10 ng/50 microL subcutaneously in the abdominal skin produced a strong inflammatory reaction, as evidenced by Evans blue dye, greater than FMLP (10(-6) mol/L) (approximately 57%); while MCP-1, 10 ng/50 microL was less effective than FMLP (10(-6) mol/L) (approximately 54%) [15].
• DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal injury in adriamycin nephropathy [17].
• RANTES: a new prostaglandin dependent endogenous pyrogen in the rat [18].

Regulatory relationships of Ccl5

• LPS downregulated the expression of MIP-1alpha and MCP-1 mRNAs and upregulated RANTES mRNA in Kupffer cells at 3-h post endotoxin [19].
• TNF-alpha also induced RANTES gene expression but LPS did not [20].
• These results provide strong evidence for the existence of rapid mechanisms in the AH/POA which involve both COX isozymes during the fever induced by RANTES, and further support the existence of an alternative PG-independent pathway in the febrile response [21].
• Altogether, these results demonstrated that infection of glial cells by JEV provided the early ERK-, NF-kappaB-, and NF-IL-6-mediated signals that directly activated RANTES expression, which might be involved in the initiation and amplification of inflammatory responses in the CNS [22].

Other interactions of Ccl5

• Treatment of rats with anti-rat MCP-1 or anti-rat RANTES had no effect on the development of lung injury [1].
• In general, CC chemokines (MCP-1, MIP-1alpha, RANTES) are chemoattractants for mononuclear cells and CXC (CINC-1, MIP-2alpha) for polymorphonuclear cells (PMNs) [23].
• Peritoneal macrophages (PM) also migrated in response to AEC-CM and each of the recombinant cytokines; however, AM were much more sensitive to AEC-CM, RANTES, and GM-CSF than were PM [24].
• To investigate the factors which regulate lymphocyte traffic in experimental autoimmune encephalomyelitis (EAE), we studied, by in situ hybridization analysis, the kinetics of mRNA expression and the potent cellular sources of RANTES, MIP-1 alpha and MIP-1 beta in the central nervous system (CNS) during the course of EAE [25].
• The mRNA expressions of T(h)1 cytokines IFN-gamma, IL-12 and tumor necrosis factor-alpha, as well as of chemokines monocyte chemotactic protein (MCP)-1 and RANTES in the spinal cord were also reduced by 76-94%, as assessed by in situ hybridization [26].

Analytical, diagnostic and therapeutic context of Ccl5

• In animals pretreated intratracheally with blocking Abs to MCP-1, RANTES, or MIP-1 beta, significant reductions in the bronchoalveolar lavage content of these chemokines occurred, suggesting that these Abs had reached their targets [1].
• Gene transfer of RANTES and MCP-1 chemokine antagonists prolongs cardiac allograft survival [27].
• Chemotactic activity for GILs and quantities of MCP-1 and RANTES were determined in allograft bronchoalveolar lavage fluid 1 wk after transplantation [12].
• RT-PCR verified by Southern blotting and sequencing of PCR products of four different C-C chemokines, macrophage-inflammatory protein-1alpha (MIP-1alpha), monocyte-chemotactic protein-1 (MCP-1), MIP-1beta, and RANTES, were performed on brain samples from EAE rats to evaluate mRNA transcription at different stages of disease [28].
• Semiquantitative RT/PCR dot-blot hybridization assay showed a 6-fold increase in mRNA for specific chemokines in the brain in cryolesion-EAE at 9 d.p.i. (MCP-1) and 11 d.p.i. (MCP-1 and MCP-5) with no significant increase in RANTES, GRO-alpha, or MIP-1alpha [29].

References