Effects of neutrophil activation and differentiation on membrane receptor mobility

• The human neutrophils comprise the first line of defence against invading microorganisms. Activation of membrane receptors for bacterial nformyl peptides, exemplified by formylmethionyl-leucyl phenylalanine (fMLF), and complement cleavage products are instrumental for neutrophil chemotaxis, phagocytosis and activation of the NADPH oxidase, generating reactive oxygen metabolites. The aim of this work was to elucidate the role of lateral mobility of membrane components for neutrophil function. Lateral mobility was measured by fluorescence recovery after photobleaching (FRAP). The results show that: i) neutrophil differentiation is accompanied by a more restricted mobility of membrane components, ii) oxidative metabolites produced by neutrophils in response to activation of protein kinase C increase the overall mobility of membrane components, iii) activation induces lateral redistribution and immobilisation of the neutrophil receptor for fMLF, and iv) internalisation of receptors is not only governed by classical signalling motifs in the receptor tail but also by receptor lateral diffusion; a fast diffusing receptor is internalised more rapidly. The effect can be shown for transfected complement receptor I (CRI) constructs, and may be exemplified in the neutrophil where activation of the fMLF receptor induces increased CRI diffusion. Finally, v) regulation of the lateral mobility of the membrane b-cytochrome appears to play a role in the activation of the neutrophil NADPH oxidase. In conclusion, the results imply that membrane domain formation and regulation of the lateral mobility of membrane components are important for neutrophil function.

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MEDICINE

MEDICIN

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