Neutrophil Immunodeficiency

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Science  12 May 2000:
Vol. 288, Issue 5468, pp. 931
DOI: 10.1126/science.288.5468.931d

Neutrophils migrate to and engulf foreign pathogens and then kill them by means of an onslaught of degradative enzymes and toxic oxygen metabolites, such as superoxide.

Ambruso et al. report the identification of a mutation in the small GTPase Rac2, the most abundant form of Rac in neutrophils, in an infant suffering from chronic severe bacterial infections. A mutation from Asp57 to Asn57 in one of the patient's Rac2 genes inhibits GTP binding and thus reduces formation of the activated, GTP-Rac2 complex. Neutrophils from the patient were defective for chemotactic response and for the production of myeloperoxidase and reactive oxygen species. Mice deficient in Rac2 have been reported to exhibit impaired neutrophil function but normal oxidase activity, suggesting that murine Rac1 protein may compensate for the absence of Rac2 and that the mutated Rac2 protein in the patient may exert a dominant negative effect in neutrophil signaling and activation, leading to immunodeficiency.—JN

Proc. Natl. Acad. Sci. U.S.A.97, 4654 (2000).

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