Th1 versus Th2 Chemokine Receptor Profiles

Although there are exceptions to the rule (1), differential chemokine receptor expression tends to be present under Th1 and Th2 inflammatory conditions. Under Th1 conditions, CXCR3 and, to a lesser extent, CCR5 predominate. Conversely, under Th2 conditions, CCR3, CCR4, and CCR8 are preferentially expressed. Thus, under Th1-promoting conditions, CXCR3 ligands including 10 kDa interferon-gamma-induced protein (IP-10) CXCL9, gamma interferon-induced monokine (MIG) CXCL10, and interferon-inducible...

Chemokine Receptor Interactions

The identification of GPCRs as chemokine receptors led to the expectation that small-molecule antagonists (or agonists) would be easier to identify and develop into drugs for diseases caused by dysregulation of these proteins (43). This expectation was complicated by the realization that chemokine receptors display a great deal of redundancy, with different receptors having overlapping activities. Moreover, multiple chemokines can activate the same receptor. The possibility was suggested that...

Ccr5

Aggressive natural killer (NK) cell leukemia is associated with a poor outcome, likely because of the multiorgan infiltration by the malignant NK cells (39). Whereas normal human NK cells and those from less aggressive lympho-proliferative diseases were negative for CCR5, unless activated with IL-2 and IL-15, malignant NK cells from the aggressive leukemia were simultaneously positive for CXCR1 and CCR5 and showed enhanced chemotaxis toward CXCR1 and CCR5 ligands. These data suggest that...

Regulation of Survival and Proliferation of Hematopoietic Stem and Progenitor Cells by Chemokines

In 1989, it was reported that chemokines CCL3 (also called MIP-1a) and CCL4 (also called regulated upon activation, normal T-cell expressed and secreted (RANTES)) have an enhancing effect on colony formation of late myeloid progenitors induced by M-CSF or GM-CSF (6). However, when stimulated by multiple cytokines such as GM-CSF, SCF, and erythropoietin (EPO), it was found that CCL3 inhibited proliferation of early progenitors such as colony-forming unit granulocyte erythrocyte monocytes...

IL8GRO and CXCR2

IL-8 CXCL8 is a member of the CXC subfamily that was initially characterized as being chemotactic for neutrophils (94,98,99). It is now recognized that IL-8 is elaborated by many cell types including many that are involved in ath-erogenesis monocytes and macrophages (including foam cells) (3,100-104), endothelial cells (3,100,101,104), and vascular smooth muscle cells (100,105). IL-8 binds with high affinity to CXCR1 and CXCR2 (106-108), both of which were first described on neutrophils...

The CXC Chemokines

The CXC chemokines can be divided into two groups on the basis of a structure function domain consisting of the presence or absence of three amino acid residues (Glu-Leu-Arg ELR motif) that precedes the first cysteine amino acid residue in the primary structure of these cytokines. The ELR+ CXC che-mokines are chemoattractants for neutrophils and act as potent angiogenic factors (6). In contrast, the ELR-CXC chemokines are chemoattractants for mononuclear cells and are potent inhibitors of...

HIV1 Tropism

Genotypic and phenotypic variation is a hallmark of HIV-1 infection. The ability of the virus to infect different cell types varies from one isolate to the next and is referred to as cellular tropism, or cytotropism. Initially, HIV-1 isolates were classified as M-tropic (able to infect primary human macrophages and CD4+ lymphocytes), T-tropic (infecting primary CD4+ T cells and T cell lines but not macrophages), and dual-tropic (capable of infecting all three cellular targets). In general,...

Nicholas W Lukacs PhD

Department of Pathology and Graduate Program in Immunology University of Michigan Medical School Ann Arbor, MI 2007 Humana Press Inc., a division of Springer Science+Business Media, LLC 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 For additional copies, pricing for bulk purchases, and or information about other Humana titles, contact Humana at the above address or at any of the following numbers Tel. 973-256-1699 Fax 973-256-8341, E-mail order humanapr.com or visit our Website http...

Tzanko S Stantchev and Christopher C Broder

There have been tremendous advances made toward our understanding of chemokine receptor biology over the past decade. Much of the research conducted in this area was fueled by discoveries that certain chemokine receptor ligands (chemokines) could specifically block human immunodeficiency virus type 1 (HIV-1) infection and that certain chemokine receptors were the long-sought coreceptors that, together with CD4, were required for the productive entry of HIV-1, HIV-2, and simian immunodeficiency...

What Is the Significance of Rho GTPases in TLymphocyte Migration

Although PI3K activation seems to be a conserved biochemical response common to most chemokines, it is now clear that this can be a dispensable signal for directional migration of T cells 14,22-24 . In many cell types e.g., endothelial cells, monocytes , the small GTPases Rho, Rac, and cdc42 play key roles in regulating the morphology of migrating cells via effects on the actin cytoskel-eton 5 . The effects of Rac and cdc42 are in turn mediated by a family of regulatory proteins including...

Gerard J Graham and Robert J Nibbs

To date, all mammalian chemokine receptors and chemokine-binding proteins belong to the seven-transmembrane 7TM -spanning family of receptors, which are typically, although not exclusively, coupled to G proteins 1 . The large G protein-coupled receptor GPCR family comprises almost 1000 members in the human genome 2,3 accounting for in excess of 3 of transcribed sequences. This family is subdivided into the class A, B, C, and F S families on the basis of shared motifs, and chemokine receptors...

Chemokine Receptor Dimerization

It has become apparent in recent years that most GPCRs are able to form dimers and other higher order oligomers 68 . This conclusion has been reached primarily using heterologous expression systems and by exploiting an array of different methodologies from coimmunoprecipitation and chemical cross-linking to, more recently, biophysical techniques such as bioluminescence resonance energy transfer BRET and fluorescence resonance energy transfer FRET . These techniques have also been used to...

CXC Chemokine Receptors 1621 CXCR4

Muller et al. performed a comprehensive examination of chemokine receptor expression on a series of breast cancer and melanoma cell lines 2 . Using quantitative RT-PCR and specific probes for CXCR1-5, CCR1-10, CX3CR1, and XCR1, seven breast cancer cell lines expressed mRNA primarily for CXCR4, CXCR2, and CCR7. In comparison with normal mammary epithelial cultures, CXCR4 and CCR7 were consistently elevated in malignant cell lines. Like breast cancer cell lines, melanoma cell lines also expressed...

Chemokines and the Directed Recruitment of Leukocytes into Allografts

Until recently, it has been difficult to dissect the relative role of each chemokine in the inflammatory processes leading to allograft rejection, especially as many chemokines and chemokine receptors are seemingly redundant 2,8 . Indeed, during allograft rejection, the expression of many chemokines and chemokine receptors can be detected in the allograft only a few of which represent viable targets for therapeutic intervention 5,6 . Chemokine regulation of leukocyte migration occurs within a...