Polymorphonuclear leukocyte-platelet interaction: role of P-selectin in thromboxane B2 and leukotriene C4 cooperative synthesis.
In PMN/platelet suspensions stimulated by fMLP giant mixed aggregates are formed and TxB2 and LTC4 are synthesized as the result of the cooperation in the arachidonic acid (AA) metabolism during cell/cell contact. PMN-derived cathepsin G induced the expression of P-selectin on platelet surface. GE12, an antibody against P-selectin, significantly reduced mixed cell aggregates. GE12 did not affect platelet aggregation induced by PMN-derived supernatants, indicating that the inhibitory effect of GE12 on mixed cell aggregation depends on inhibition of PMN/platelet adhesion. GE12 significantly reduced TxB2 and LTC4 production in PMN/platelet mixed cell suspensions stimulated by fMLP. As previously reported, synthesis of 3H-TxB2 in 3H-AA-labeled PMN/unlabeled platelets indicates that platelets utilize 3H-AA from PMN. 3H-LTC4 production in unlabeled PMN/3H-AA-labeled platelets indicates that bidirectional routes are utilized in this system for LTC4 synthesis. GE12 significantly reduced 3H-TxB2 and 3H-LTC4 synthesis. These results show that cathepsin G released by activated PMN induces the expression of P-selectin on platelet membrane: this adhesive glycoprotein modulates cell-cell contact and transcellular metabolism of AA.
Maugeri
N
N
Giulio Bizzozero Laboratory of Platelet and Leukocyte Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Evangelista
V
V
Celardo
A
A
Dell'Elba
G
G
Martelli
N
N
Piccardoni
P
P
de Gaetano
G
G
Cerletti
C
C
D000595:Amino Acid Sequence; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002240:Carbohydrate Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D003571:Cytochalasin B / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D012697:Serine Endopeptidases; D012701:Serotonin / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis*
D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D016718:Arachidonic Acid; D017997:Leukotriene C4; D012701:Serotonin; D003571:Cytochalasin B; D013929:Thromboxane B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G