Eicosanoid production from porcine neutrophils and platelets: differential production with various agonists.
Polymorphonuclear neutrophils (PMN) and platelets interact to produce both inflammatory and anti-inflammatory lipid mediators during human disease. Because swine models of human disease are used, it is important to understand the mechanisms involved in the formation of lipid mediators from porcine PMN-platelet interactions. In the present study, we investigated the mechanism of thromboxane (Tx) A2 and lipoxin A4 (LXA4) formation from porcine PMN and platelets, respectively. PMN (10(7)/ml) and platelet (30 x 10(7)/ml) suspensions stimulated with porcine C5a (pC5a), but not recombinant human C5a (rhC5a), significantly enhanced TxB2 formation. After cytochalasin B treatment, pC5a or rhC5a significantly and equally enhanced TxB2 formation from PMN-platelet suspensions. A-23187-induced TxB2 formation from platelets was not significantly augmented by the presence of PMN in these suspensions. A-23187 induced significant LXA4 production from porcine PMN that was not augmented by addition of platelets. Flow cytometric analysis of PMN-platelet suspensions revealed activated platelets adherent to PMN following pC5a stimulation. CV-6209, a platelet-activating factor (PAF) receptor antagonist, dose dependently prevented pC5a-induced platelet adherence to PMN and TxB2 formation. These data demonstrate that 1) porcine PMN alone can biosynthesize LXA4 without the assistance of platelets, which is in sharp contrast to human PMN-platelet interactions, and 2) in the absence of cytochalasin B, pC5a stimulates PAF biosynthesis from porcine PMN, resulting in TxB2 formation from platelets.
Stahl
G L
GL
Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Morse
D S
DS
Martin
S L
SL
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002450:Cell Communication; D015936:Complement C5a / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology; D015777:Eicosanoids / Q000097:blood*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D066298:In Vitro Techniques; D044045:Lipoxins; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000097:blood
D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D011994:Recombinant Proteins; C040527:lipoxin A4; C053321:CV 6209; D000001:Calcimycin; D003571:Cytochalasin B; D013928:Thromboxane A2; D015936:Complement C5a