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Chapter 5 : Chemokines and Phagocyte Trafficking
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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Phagocytosing neutrophils produce chemoattractants themselves to continue cell recruitment after the initial phase driven by C5a. The chemokines are important in providing varying degrees of cell type specificity to leukocyte recruitment. C5a and LTB4 are potent neutrophil chemoattractants (others are platelet-activating factor and formyl peptides derived from bacteria). The specificity of different chemokines for leukocyte types provides a mechanism to explain the geographical organization of the immune system under basal conditions and the recruitment of selected leukocyte types in response to different inflammatory stimuli. Chemokine receptors are approximately 350 amino acids long, having an N-terminal extracellular domain followed by seven hydrophobic domains that traverse the plasma membrane leaving a cytoplasmic tail. IL-8 is considered the prototypic neutrophil-selective CXC chemokine. ELR+ CXC chemokines and their receptors play a direct role in the pathogenesis of a number of inflammatory diseases, including reperfusion injury, ulcerative colitis, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). Lymphatic filariasis is a chronic human parasitic disease in which the parasites repeatedly provoke both acute and chronic inflammatory reactions in the lymphatics and bloodstream. Chemokine receptor expression on macrophages is also altered in hypoxic tissue microenvironments, such as the necrotic areas of tumors or in ischemic tissues. The usual caveats apply as with any anti-inflammatory therapy concerning compromising host defense processes.
The ELR+ CXC chemokines and their binding to chemokine receptors on neutrophils.
The dynamic expression of chemokine receptors on neutrophils as they age.
The role of the CXCL12/CXCR4 chemokine axis in neutrophil clearance via the bone marrow.
Monocyte subsets and their expression of chemokine receptors
Differential profiles of chemokine production by classically and alternatively activated macrophages