Stimulus-response coupling in fresh and stored granulocytes.
Granulocytes stored in the blood bank prior to transfusion undergo progressive decrements in their ability to circulate and migrate in vivo and to migrate in vitro (chemotaxis). The pathogenesis of granulocyte (PMN) chemotaxis (CTX) dysfunction after room-temperature storage of PMN is unclear. Previous work in the authors' laboratory and others led to the hypothesis that intracellular transmission of chemotactic signals, referred to as stimulus-response coupling (SRC), might be abnormal in stored PMN. This report presents an investigation of the ability of fresh and stored PMN to generate and respond to leukotriene-B4 (LTB4), the chief intracellular amplifier of SRC for CTX. PMN were sampled from concentrates within 4 hours of collection and after 24 and 48 hours of storage in transfer packs at room temperature (RT). Fresh, stimulated PMN synthesized 202 +/- 51 ng of LTB4 and 110 +/- 11 ng of 5-hydroxyeicosatetraenoic acid (HETE) per 10(7) PMN. Synthesis of LTB4, but not HETE was significantly decreased after 24 hours' storage, and LTB4 and HETE synthesis decreased after 48 hours. The incubation of stored PMN with arachidonic acid (AA) maintained levels of LTB4 synthesis in PMN stored for 24 but not 48 hours. Also, the CTX defect of stored PMN to F-Met-Leu-Phe (FMLP) was not improved by the supplementation of PMN with exogenous sources of LTB4 or AA.(ABSTRACT TRUNCATED AT 250 WORDS)
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Laboratory Service, Veterans Administration Medical Center, San Diego, California.
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D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001800:Blood Specimen Collection / Q000379:methods; D002634:Chemotaxis, Leukocyte; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000494:pharmacology; D013696:Temperature
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid