title: Formation of lipoxins and leukotrienes during receptor-mediated interactions of human platelets and recombinant human granulocyte/macrophage colony-stimulating factor-primed neutrophils.
abstract: The generation of lipoxygenase products of arachidonic acid is considered an important event in inflammation. This study demonstrates the levels of both lipoxins and leukotrienes (LTC4, LTD4, LTB4, and omega-oxidized LTB4) generated from endogenous sources of arachidonate by PMN primed with recombinant human granulocyte/macrophage colony-stimulating factor and in coincubations with platelets (1:1 to 1:100 ratio). Upon exposure to receptor-mediated stimuli (FMLP and thrombin), the levels of lipoxins generated were within the range of both LTB4 and LTC4. Co-incubation of [1-14C]arachidonate-labeled platelets with primed polymorphonuclear leukocytes (PMN) followed by addition of thrombin and FMLP led to the formation of both 5- and 15-LO products that carried 14C label. Thus, in addition to the transcellular conversion of LTA4 to platelet-derived lipoxins and LTC4, PMN can use platelet-derived arachidonate to generate lipoxygenase products. These results are the first to document the relationship between the levels of lipoxins and leukotrienes generated by receptor-mediated activation of cytokineprimed PMN interacting with platelets. Moreover, they indicate that PMN-platelet interactions utilize bidirectional transcellular routes to contribute to lipoxin formation.
authors.affiliation: Hematology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: S
authors.initials: S
authors.lastname: Fiore
authors.forename: C N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D015289:Leukotrienes; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013917:Thrombin