Cellular activation, chemokines

Cellular Activation. Chemokines are potent cell activators after binding to the appropriate G protein-linked, seven-transmembrane spanning receptors, chemokines elicit transient intracellular calcium flux, actin polymerization, oxidative burst with release of superoxide free radicals, exocytosis of secondary granule constituents, and increased avidity of integrins for their adhesion molecules (Dl, E2). 

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

A plethora of signaling molecules—acting in a tailored, concerted fashion—are involved in directing cellular activities and cell-to-cell communication, affecting a wide variety of cell behaviors including migration, adhesion, activation, proliferation, differentiation, and fusion—all important toward the establishment of a FBR in vivo. Chemokines are a superfamily of polypeptides and a subset of the larger class of... 

Chemokines have been implicated in diverse pathophysiological functions in allergic inflammation including chemoattraction, cellular activation, hematopoiesis, homeostatic role, and modulation of T cell immune response (R6). 

Liao F, Shirakawa AK, Foley JF, Rabin RL, Farber JM Human B cells become highly responsive to macrophage-inflammatory protein-3 alpha/CC chemokine ligand-20 after cellular activation without changes in CCR6 expression or ligand binding. J Immunol 2002 168 4871 880. 

The HIV-1 coreceptors CXCR4 and CCR5 bind to ligand members of a family of molecules known as chemokines, or chemotactic cytokines. While the hallmark function of these small proteins is the direction of leukocyte trafficking, they can also participate in cellular events such as activation and costimulation (Bajetto et al. 2(X)la). Members of the chemokine family can be classified as either homeostatic or inflammatory based on their temporal expression (Charo and Ransohoff 2006 Kim 2005). Although traditionally the CNS had been thought to be protected from immune acti-... 

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