Neutrophils play a pivotal role in host defense. During an immune response, these cells adhere to the vessel wall, migrate to sites of inflammation in the tissues, and kill and remove the infectious organism or foreign body. We are investigating the intracellular signals in neutrophils that control the process of adherence, chemotaxis, secretion, and phagocytosis. In particular, emphasis is placed upon the regulatory role of cyclic nucleotide-dependent protein kinases on the structural organization and sites of modification during cell activation. Immunofluorescence staining of microtubules in human neutrophils.
Microtubules organize at the microtubule organizing center and extend to the plasma membrane.
Microtubules are believed to organize the shape of the neutrophil during chemotaxis, and the cytoplasmic granules during phagocytosis and secretion. We are investigating the signals that regulate the structural organization of microtubules with intermediate filaments and granules in activated neutrophils. Scanning electron micrograph of a neutrophil in the process of ingesting yeast. Killing of microorganisms by neutrophils involves the release of digestive and microbiocidal agents into the phagosome during granule fusion with the phagosome. We are investigating the mechanisms for cAMP specific phosphodiesterase regulation of neutrophil activation.