Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca2+- ionophore A-23187 (0.5 μmol/L) for 30', accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 μmol/L) or by heart pretreatment with the LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL- derived 5-lipoxygenase (5-LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage- colony stimulating factor-primed PMNL challenged with the tripeptide n- formyl-methionyl-leucyl-phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alterations observed.

Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit / A. Sala, G. Aliev, G. Rossoni, F. Berti, C. Buccellati, G. Burnstock, G. Folco, J. Maclouf. - In: BLOOD. - ISSN 0006-4971. - 87:5(1996), pp. 1824-1832.

Morphological and functional changes of coronary vasculature caused by transcellular biosynthesis of sulfidopeptide leukotrienes in isolated heart of rabbit

A. Sala
Primo
;
G. Rossoni;C. Buccellati;
1996

Abstract

Morphological and functional modifications occurring in Langendorff rabbit heart preparations perfused with purified human leukocytes (PMNL), as an organ model of sulfidopeptide-leukotrienes (sLT) transcellular biosynthesis, were studied. Coronary perfusion pressure (CPP), monitored as an index of coronary vasospasm, increased by 295% after challenge with the Ca2+- ionophore A-23187 (0.5 μmol/L) for 30', accompanied by a significant formation of sLT. Increase in CPP was prevented by PMNL pretreatment with the 5-lipoxygenase inhibitor MK-886 (1 μmol/L) or by heart pretreatment with the LTD4-receptor antagonist SKF 104353, indicating a pivotal role of PMNL- derived 5-lipoxygenase (5-LO) products in the observed functional modifications. Similar effects were obtained using granulocyte macrophage- colony stimulating factor-primed PMNL challenged with the tripeptide n- formyl-methionyl-leucyl-phenylalanine. Scanning electron microscopy (SEM) of coronary arteries showed craters on the vessel luminal surface, PMNL adhering to endothelial cells (EC), increased number of microvilli on EC, presence of nonviable, desquamating, fusiform EC. SEM and transmission electron microscopy of myocardial microvessels, showed presence of perivascular and intermuscle edema, presence of activated PMNL and decreased number of patent microvessels. These morphological alterations were significantly blunted by MK-886 or SKF 104353. These data provide evidence of close interaction between PMNL and myocardial EC, resulting in enhanced sLT formation via transcellular biosynthesis, originating from transfer of PMNL-derived LTA4 to EC. These potent proinflammatory autacoids are responsible for coronary vasospasm and the morphological alterations observed.
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/180862
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 61
  • ???jsp.display-item.citation.isi??? ND
social impact