Chemokines leukocyte migration

Paoletti S, Petkovic V, Sebastiani S, Danelon MG, Uguccioni M, Gerber BO. A rich chemokine environment strongly enhances leukocyte migration and activities. Blood 2005 105(9) 3405-3412. 

Figure 31.5. Leukocyte migration into focally ischemic brain. Histologic and schematic representations of changes in leukocyte behavior in die brain microvessels after focal ischemia. Shortly (widhn l-6h) after experimental stroke, many of die leukocytes, primaiily neuti ophils, in die ischemic dssue vessels are adherent to die post-capillai y venuole and capillai y walls. Tliis can modify and exacerbate die decreased blood flow occuriing in die already ischemic brain. Tlien, diese neuti ophils can find dieir way outside die vascular walls into die focal ischemic cortex over die next 6-24h. Macrophages move into die brain later (i.e., over 1—5 days) and significantly accumulate in die infai cted brain. These changes in leukocyte behavior ai e mediated by increased brain inflammatory cytokine, adliesion molecule(s), and chemokine expression in die ischemic/injured brain. Reproduced from ref Barone FC, Feuerstein GZ. Inflammatory mediators and stroke new opportunities for novel therapeutics. J Cereb Blood Flow Me tab 1999 19 819-834. With permission from Nature.

Moser B, Wolf M, Walz A, Loetscher P. Chemokines multiple levels of leukocyte migration control. Trends Immunol 2004 25 75-84. 

Chemokines are a superfamily of small proteins which play a crucial role in immune and inflammatory reactions and in viral infection (Hedrick and Zlotnik, 1996 Baggi-olini et al, 1997 Rollins, 1997). Most chemokines cause migration of leukocytes, but these molecules also affect angiogenesis, proliferation of hematopoietic precursors, and viral responses. Based on a cysteine motif, a CXC, CC, C and CX3C family have been identified (Fig. 1). CXC (or a) chemokines are active on neutrophils and lymphocytes while CC (or (3) chemokines exert their action on multiple leukocyte subtypes, including monocytes, basophils, eosinophils, T-lymphocytes, dendritic cells (DC) and NK cells, but they are generally inactive on PMN. Eotaxins... 

Chemokines, c/jemoattractant cytokines, are small (8—14 kDa) proteins that bind to G-protein-coupled receptors composed of seven transmembrane domains (BaggioHni, 1998). The chemokine family encompasses more than 50 members, which can be either homeostatic or inflammatory (Zlotnik Yoshie, 2000). The former are constitutively expressed in certain tissues and have roles in tissue development, such as angiogenesis or neovascularization, or basal leukocyte migration (Rot von Andrian, 2004). In the latter, an infection or other proinflammatory stimulus (TNF-a) will cause the release of chemokines that will direct the recruitment of leukocytes (e.g., neutrophils, monocytes, etc.) toward the site of inflammation (Zlotnik, Burkhardt, Homey, 2011). 

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