Biological activities of Lipoxin A include lung strip contraction and dilation of arterioles <i>in wiwo</i>

Dahlén, Sven‐Erik; Raud, J.; Serhan, Charles N.; Björk, Jakob; Samuelsson, Bengt

doi:10.1111/j.1748-1716.1987.tb08187.x

Cited by 78 publications

(25 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, at submicromolar concentrations, lipoxins stimulate endothelial-dependent relaxation of aortic strips (41). LXA4 also provokes vasodilation (in vivo) (42)(43)(44) and stimulates the formation of prostacyclin by human endothelial cells, albeit at higher concentrations (45). In addition to extracellular roles, LXA4 may also serve an intracellular function since it activates isolated protein kinase C (46) and selectively stimulates its 'y-subspecies (47).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, they suggest that lipoxins can also be formed after initial oxygenation by the 5-LO and transcellular metabolism. Since lipoxins have been found to possess vasoactive functions (41)(42)(43)(44)(45), their formation during the interaction of PMNs with platelets may have implications in the regulation of hemostasis, inflammation, and the interactions of these cells with the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro.

Serhan¹,

Sheppard²

1990

J. Clin. Invest.

283

182

View full text Add to dashboard Cite

Human neutrophils from peripheral blood may physically interact with platelets in several settings including hemostasis, inflammation, and a variety of vascular disorders. A role for lipoxygenase (LO)-derived products has been implicated in each of these events; therefore, we investigated the formation of lipoxins during coincubation of human neutrophils and platelets. Simultaneous addition of FMLP and thrombin to coincubations of these cells led to formation of both lipoxin A4 and lipoxin B4, which were monitored by reversed-phase high pressure liquid chromatography. Neither stimulus nor cell type alone induced the formation of these products. When leukotriene A, (LTA4), a candidate for the transmitting signal, was added to platelets, lipoxins were formed. In cell-free 100,000 g supernatants of platelet lysates, which displayed 12-LO activity, LTA4 was also transformed to lipoxins. Platelet formation

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro.

Serhan¹,

Sheppard²

1990

J. Clin. Invest.

283

182

View full text Add to dashboard Cite

show abstract

“…One possible mechanism is the recruitment and activation of neutrophils, through the 15-lipoxygenase pathway, by airway epithelial cells [43][44][45][46][47]. Another system implicated in airway inflammatory responses, which could be triggered by the alteration of the epithelial surface, is the sensory nerves.…”

Section: Airway Epithelial Damagementioning

confidence: 99%

Morphological and cellular basis for airflow limitation in smokers

Saetta¹,

Finkelstein²,

Mg³

1994

Eur Respir J

100

View full text Add to dashboard Cite

M Mo or rp ph ho ol lo og gi ic ca al l a an nd d c ce el ll lu ul la ar r b ba as si is s f fo or r a ai ir rf fl lo ow w l li im mi it ta at ti io on n i in n s sm mo ok ke er rs s ABSTRACT: Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways <400 µm in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV 1 ). The pathological changes found in smokers, that could be responsible for active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) structural changes in the airway wall; and 4) loss of alveolar attachments.However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV 1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways.We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of α 1 -antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.

show abstract

“…More recently, LxA4 has been shown to contract pulmonary smooth muscle (i.e., guinea pig lung) and to relax vascular smooth muscle (8) at concentrations <1 ,uM. Dahlen et al (8) further showed that LxA4 had no significant myotropic activity on either guinea pig trachea or guinea pig ileum (8).…”

mentioning

confidence: 98%

Lipoxins A4 and B4: comparison of icosanoids having bronchoconstrictor and vasodilator actions but lacking platelet aggregatory activity.

Lefer

Stahl

Lefer

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lipoxins A4 (LxA4) and B4 (LxB4), two lipoxygenase-generated icosanoids of arachidonic acid metabolism, were found to have a distinct biological profile. Both LxA4 and LxB4 slowly contracted pulmonary parenchymal strips isolated from guinea pigs, rabbits, and rats in a concentration-dependent manner over the range 0.1-1 IAM. This bronchoconstrictor effect was not associated with release of peptide leukotrienes or thromboxane A2, nor was it blocked by lipoxygenase inhibitors or thromboxane receptor antagonists, suggesting it is a direct effect of lipoxins. However, the leukotriene D4 (LTD4) receptor antagonist LY-171883 reduced the LxA4 response, indicating that LTD4 and LxA4 may share the same receptor. LxA4 and LxB4 also exerted an endothelium-dependent vasorelaxation in guinea pig, rat, and, to a lesser extent, rabbit aortic vascular smooth muscle. In contrast to other vasoactive icosanoids, LxA4 and LxB4 failed to aggregate rat, rabbit, or guinea pig platelets or to inhibit ADP-induced aggregation. LxA4 also enhanced the release of liver lysosomal hydrolases in a liver large granule fraction, indicating a lysosomal labilizing action of LxA4. LxA4 and LxB4 share a similar biological profile. It is not clear yet whether the lipoxins could be mediators of circulatory or pulmonary disease states.The lipoxins are a class of biologically active trihydroxy lipids having a conjugated tetraene and are formed within the arachidonic acid cascade. Lipoxins A and B, the two major lipoxins, have been described by Serhan et al. (1,2). These icosanoids are formed by an interesting biosynthetic sequence first involving oxygenation of arachidonic acid by a 15-lipoxygenase and subsequent oxygenation by a dual function 5-lipoxygenase involving oxidation and dehydration to give a 5,6-epoxytetraene. This epoxide is then opened by attack at the more electrophilic 6-position by an epoxide hydrolase yielding lipoxin A (1) or via conjugate attack of the hydrolase at the 14-position generating lipoxin B (1). These icosanoids have been given the trivial name "lipoxin" (short for "lipoxygenation interaction products") because of the unique interaction of two lipoxygenases in their biosynthesis (1, 2). These biosynthetic events appear to occur in certain types of leukocytes, including neutrophils and eosinophils (2). Recently, the structures of lipoxins A and B have been verified by total synthesis (3, 4). Now that the structures and biosynthesis of the lipoxins are known, their nomenclature has been established, and these substances have been termed lipoxin A4 and lipoxin B4 (5).Very little is known about the biological activity of lipoxins A4 (LxA4) and B4 (LxB4). Early findings showed that LxA4 activated protein kinase C in vitro and therefore may serve as an activator of intracellular events in smooth muscle cells (6). Secondly, LxA4 has been shown to induce leukocyte lysosomal membrane leakiness and to release lysosomal hydrolases and superoxide free radicals (7). Immunologically, LxA4 and LxB4 block the action of natural kil...

show abstract

Biological activities of Lipoxin A include lung strip contraction and dilation of arterioles in wiwo

Cited by 78 publications

References 10 publications

Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro.

Lipoxin formation during human neutrophil-platelet interactions. Evidence for the transformation of leukotriene A4 by platelet 12-lipoxygenase in vitro.

Morphological and cellular basis for airflow limitation in smokers

Lipoxins A4 and B4: comparison of icosanoids having bronchoconstrictor and vasodilator actions but lacking platelet aggregatory activity.

Contact Info

Product

Resources

About