9710433

pubmed:Citation

4

Neutrophil (PMN) dysfunction occurs in HIV infection. Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway that play a role in host defense and are synthesized by PMN. We investigated the synthesis of LT by PMN from HIV-infected subjects. There was a reduction (4.0+/-1.3% of control) in LT synthesis in PMN from HIV-infected compared with normal subjects. This was associated with reduced expression of 5-LO-activating protein (31.2+/-9.6% of normal), but not of 5-LO itself. Since HIV does not directly infect PMN, we considered that these effects were due to reduced release of cytokines, such as granulocyte colony-stimulating factor (G-CSF). We examined the effect of G-CSF treatment (300 microgram daily for 5 d) on eight HIV-infected subjects. PMN were studied in vitro before therapy (day 1) and on days 4 and 7. LTB4 synthesis was increased on day 4 of G-CSF treatment, and returned toward day 1 levels on day 7. 5-LO and 5-LO-activating protein expression were increased in parallel. As a functional correlate to this increase in PMN LT synthesis by G-CSF, we examined the effects on killing of Cryptococcus neoformans. Anticryptococcal activity of PMN from HIV-infected subjects was less than that of PMN from normal subjects. G-CSF treatment improved fungistatic activity of PMN. This increase in antifungal activity was attenuated by in vitro treatment with the LT synthesis inhibitor, MK-886. In conclusion, PMN from HIV-infected subjects demonstrate reduced 5-LO metabolism and antifungal activity in vitro, which was reversed by in vivo G-CSF therapy.

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http://linkedlifedata.com/resource/pubmed/journal/7802877

http://linkedlifedata.com/resource/pubmed/chemical/5-Lipoxygenase-Activating Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ALOX5AP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase, http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte Colony-Stimulating..., http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4, http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins

Aug

pubmed-author:CoffeyM JMJ, pubmed-author:GeorgeSS, pubmed-author:KazanjianP HPH, pubmed-author:Peters-GoldenMM, pubmed-author:PhareS MSM

15

NLM

663-70

pubmed-meshheading:9710433-5-Lipoxygenase-Activating Proteins, pubmed-meshheading:9710433-AIDS-Related Opportunistic Infections, pubmed-meshheading:9710433-Arachidonate 5-Lipoxygenase, pubmed-meshheading:9710433-Arachidonic Acid, pubmed-meshheading:9710433-Carrier Proteins, pubmed-meshheading:9710433-Cryptococcus neoformans, pubmed-meshheading:9710433-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:9710433-HIV Infections, pubmed-meshheading:9710433-Humans, pubmed-meshheading:9710433-Immunity, Cellular, pubmed-meshheading:9710433-Leukotriene B4, pubmed-meshheading:9710433-Leukotrienes, pubmed-meshheading:9710433-Membrane Proteins, pubmed-meshheading:9710433-Neutrophils, pubmed-meshheading:9710433-Prospective Studies

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.