Original Articles Cathepsin G Degrades Denatured Collagen

Inflammation

, Volume 13, Issue 2, pp 163-174

First online:

Lysophosphatides enhance superoxide responses of stimulated human neutrophils

  • Isaac GinsburgAffiliated withDepartment of Oral Biology, Hebrew University-Hadassah School of Dental Medicine Founded by the Alpha Omega Fraternity
  • , Peter A. WardAffiliated withDepartment of Pathology, University of Michigan
  • , James VaraniAffiliated withDepartment of Pathology, University of Michigan

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Abstract

Human neutrophils which are pretreated with subtoxic concentrations of a variety of lysophosphatides (lysophosphatidytcholine, lysophosphatidylcholine oleoyl, lysophosphatidylcholine myrioyl, lysophosphatidylcholine stearoyl, lysophosphatidylcholine gamma-O-hexadecyl, lysophosphatidylinositol, and lysophosphatidylglycerol) act synergistically with neutrophil agonists phorbol myristate acetate, immune complexes, poly-L-histidine, phytohemagglutinin, andN-formyl methionyl-leucyl-phenyalanine to cause enhanced generation of superoxide (O 2 ). None of the lyso compounds by themselves caused generation of O 2 . The lyso compounds strongly bound to the neutrophils and could not be washed away. All of the lyso compounds that collaborated with agonists to stimulate O 2 generation were hemolytic for human red blood cells. On the other hand, lyso compounds that were nonhemolytic for red blood cells (lysophosphatidylcholine caproate, lysophosphatidylcholine decanoyl, lysophosphatidylethanolamine, lysophosphatidylserine) failed to collaborate with agonists to generate synergistic amounts of O 2 . However, in the presence of cytochalasin B, both lysophosphatidyiethanolamine and lysophosphatidylserine also markedly enhanced O 2 generation induced by immune complexes. O 2 generation was also very markedly enhanced when substimulatory amounts of arachidonic acid or eicosapentanoic acid were added to PMNs in the presence of a variety of agonists. On the other hand, neither phospholipase C, streptolysin S (highly hemolytic), phospholipase A2, phosphatidylcholine, nor phosphatidylcholine dipalmitoyl (all nonhemolytic) had the capacity to synergize with any of the agonists tested to generate enhanced amounts of O 2 . The data suggest that in addition to long-chain fatty acids, only those lyso compounds that possess fatty acids with more than 10 carbons and that are also highly hemolytic can cause enhanced generation of O 2 in stimulated PMNs.