Neutrophils play an important role in the host defense against infection and in a number of allergic and nonallergic tissue-damaging inflammatory reactions. They migrate from blood to the site of inflammation through the process known as chemotaxis, in response to agents liberated at the site of inflammation termed """"""""chemotactic factors"""""""". Calcium, cAMP and phospholipids and their derivatives have been considered as the possible intracellular messengers for the chemotactic activation of neutrophis. But it is not clear through what molecular mechanism the signals for the many observed metabolic alterations are achieved. An essential part for the inducing and regulating process in the functioning and responses for a variety of cells is protein phosphorylation. It is proposed to study the relation between neutrophil chemotactic activation and protein phosphorylation. (1) To define the varieties of protein kinases and their endogenous substrates in various subcellular fractions of neutrophil; (2) To define the phosphoproteins whose phosphorylation level are regulated by various chemotactic factors (f-Met-Leu-Phe, C5a and Leukotriene B4) in intact cell and to correlate the physiological responses of neutrophil to the phosphorylation level of endogenous phosphoproteins; (3) To identify the physiologically important phosphorylation systems in the neutrophil activation; (4) To search for possible regulation of the f-Met-Leu-Phe receptor protein phosphorylation; and (5) To study the possible role of vimentin phosphorylation in neutrophil chemotactic activation.
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