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Human Biology
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Chemokines Secreted proteins, 8-11 kDa with C a-helix, 3 anti-parallel b-strands, and activate GPCR and GAG Alpha or CXC: first two conserved cysteines separated, active mainly on neutrophils Beta or CC: first two conserved cysteines adjacent; active on monocytes, lymphocytes, basophils. Chemokine Receptors are 7 transmembrane glycoproteins Variable N determines chemokine specificity. Variable C determines interactions with molecules. Chemokine receptors are specific (one chemokine), shared (several chemokines of same branch) or promiscuous (multiple chemokines across branches) Fractalkine: chemoattractant AND adhesion molecule Found on activated endothelium. Surface form is a cell adhesion molecule that induces cell activation. Soluble form attracts monocytes, NK cells, and CD8+ T lymphocyte. FKN induces leukocyte capture since monocytes, CD8+ T cells, and NK cells adhere to FKN Mouse Cardiac Allotransplantation rejection Rejected grafts were harvested; immuno-stained using anti-FKN Ab and compared to isograft controls. Anti-CX3CR1 treatment prolongs cardiac allograft survival. Fractalkine expression is increased in acute renal allograft rejection. Fractalkine and CX3CR1 in Atherosclerosis FKN-- and CX3CR1-- mice have less atherogenesis Human CX3CR1 polymorphisms protect a
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