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Two distinct signaling pathways operate sequentially, thus guiding neutrophils to bacterial invaders, according to Heit et al. on page 91. Although one pathway lures neutrophils in the right general direction, the other pathway dominates when the prey is within reach.- Q' k2 B) j: g& @
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Neutrophils leave the bloodstream and migrate to infection sites by following intermediary chemokine signals (such as IL-8) that are generated by damaged host cells. End-target signals like fMLP or LPS, either released by the pathogen itself or by the body in response to the bacteria, also attract neutrophils. Since the blood cells prefer to pursue end-targets when both signals are present, the authors speculated, correctly, that different pathways controlled the two responses.
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The pathways can be distinguished by their kinase-dependence. Migration to intermediary chemoattractants depended on PI3K, which phosphorylated Akt. End-targets induced migration via p38 MAPK and inhibited Akt phosphorylation, even at low concentrations. The result is that neutrophils ignore intermediate molecules when bacteria are in the vicinity. The authors speculate that migration may change depending on the integrin subunit recruited—the CD11a recruited by PI3K may be subservient in migration competence to the CD11b recruited by p38 MAPK. The findings could explain why the leakage of bacterial products into the bloodstream can cause such severe problems, as these chemicals keep neutrophils from following intermediary signals into the surrounding tissue.(End targets win the migration battle by ) |
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发表于 2009-3-6 00:05
发表于 2015-6-3 18:29
