Chemokines

Abstract

not been systematically examined. Similar clustering has C been observed among genes encoding chemokine receptors. HEMOKINES have recently become the focus of intense interest and discussion. This has occurred, in One exception to the CC/CXC rule is lymphotactin, a part, because of an enlarging view of what chemokines do. potent attractant for T lymphocytes, but not monocytes. 4 As recently as 2 or 3 years ago a chemokine review would Although it is the right size to be a chemokine and it has have begun with a discussion of the importance of chemotacseveral characteristic sequence signatures common to CC tic factors in controlling leukocyte function and trafficking, chemokines, it has only two cysteines. Nonetheless, these and would have pointed out that specificity for leukocyte cysteines correspond to cysteines 2 and 4 of chemokines, subsets is what sets chemokines apart from other chemoatand it has been suggested that lymphotactin belongs to a tractants. For example, formylated peptides (eg, f-Met-Leuthird chemokine subfamily denoted C, because of the lone Phe), complement fragments (eg, C5a), or arachidonic acid cysteine in the N-terminal domain. Consistent with its new metabolites (eg, LTB4) attract neutrophils and monocytes assignment, lymphotactin's gene maps to 1q. So far, lymphowith equal potency, whereas some chemokines (eg, interleutactin is the only member of this putative family. kin-8 [IL-8]) attract neutrophils but have no discernible ef-Another exception is a CX 3 C chemokine (also referred to as fects on monocytes. This discrimination has led to the fre-''fractalkine'' or ''neurotactin'') that is an integral membrane quently espoused proposition that chemokines are involved protein with a chemokine domain at its N-terminus. 3,3a This in the pathogenesis of diseases having characteristic infildomain differs from other chemokines by the presence of three trates. amino acids intervening between the first two cysteines. Model-However, we now know that chemokines and their receping studies suggest that the three-dimensional structure of tors are expressed by a wide variety of nonhematopoietic chemokines (see below) can only accommodate 0, 1, or 3 cells, and that chemokine function extends far beyond leukoamino acids between the first two cysteines, explaining the cyte physiology. Even within the world of leukocytes, the absence of a CX 2 C chemokine. Like lymphotactin, the gene connections among chemokines, their receptors, and human encoding CX 3 C chemokine maps to a locus different from other immunodeficiency virus (HIV) infection broadens the prechemokines, and so far it is the sole example of a chemokine viously narrow focus on chemokines as mere chemoattracwith this structural motif. tants. Furthermore, a proliferation of animal models has more precisely defined the functions of chemokines in vivo. CXC CHEMOKINES This review will attempt to describe what is understood Discussions of chemokine function tend to look like a about chemokines in light of recent discoveries. collection of disconnected...

Immune stimulating properties of a novel polysaccharide from the medicinal plant Tinospora cordifolia

“…MCP-1 is a potent chemoattractant for monocytes and activated CD4 and CD8 T cells that is reported to induce granule release from NK and CD8+ cells, activate NK function in CD56+ cells, and act as a potent releasing factor for histamine from basophiles [41]. Furthermore, it is reported to exhibit antitumor effects by enhancing tumor specific immunity, presumably in a T-cell-dependent manner [42].…”

“…The presence of IL-12 leads to Th1 response while IL-4 leads to Th2 development and the two pathways express mutually suppressive effect as well. IL-1 is identified as an inducer of IL-12 [41] while IL-18 is an early response in the development of Th1 cells by induction of IFN-g. The cytokine profile, IL-12, IL-18, IFN-g together with IL-1 by RR1 stimulation and the dose-dependent synthesis of these cytokines clearly demonstrate the Th1 pathway which is essential for cellular immunity and killing of intracellular pathogens and malignant cells.…”

Neutrophil-derived chemokines on the road to immunity

“…CXC chemokines containing the ELR motif also display a potent angiogenic activity, while CXC chemokines lacking the ELR motif are angiostatic [2]. The CC family includes chemokines such as CCL2/monocyte chemotactic protein/MCP-1, CCL3/macrophage inflammatory protein (MIP)-1␣, CCL4/MIP-1␤, CCL5/Regulated on Activation, Normal T cells Expressed and Activated (RANTES), CCL7/MCP-3, CCL17/Thymus and activation regulated chemokine (TARC), CCL18/Pulmonary and activation regulated chemokine (PARC), CCL19/MIP-3␤ and CCL20/MIP-3␣, that are mostly chemotactic and stimulatory for monocytes, macrophages, dendritic cells (DCs), T cells, NK cells, eosinophils and basophils [1,3,4,7]. Chemokines are mostly secreted into the extracellular space as soluble factors or bound to the extracellular matrix, thus forming transient or stable concentration gradients, respectively [1].…”

Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response

“…In the EIAV LN40 -infected group, IL-6 was positively correlated with the viral RNA copy numbers (r = 0.660, P = 0.003), but two cytokines, IFN-␤ (r = −0.689, P = 0.002) and IL-1␤ (r = −0.687, P = 0.002), were negatively correlated ( Table 2). In addition, chemokines mediate cell migration and the recruitment of leukocytes, which process and secrete cytokines and chemokines, which regulate distinct intracellular signaling events (Baggiolini, 1998;Rollins, 1997). Thus, we examined the possible correlations among the expression of cytokines/chemokines at corresponding sites.…”