Chemokinetic activity of arachidonic acid lipoxygenase products on leuocyctes of different species

Palmer, Richard; Stepney, Ray; Higgs, G. A.; Eakins, Kenneth E.

doi:10.1016/s0090-6980(80)80058-x

Cited by 398 publications

(86 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a potent chemoattractant for human neutrophils and also has chemotactic activity for monocytes (2)(3)(4)(5)(6). LTB 4 exerts this activity via a G protein-coupled receptor in target cells (7) and induces a cascade of cellular events that amplify the inflammatory response (8).…”

Section: Leukotriene B 4 (Ltb 4 )mentioning

confidence: 99%

Expression of the CYP4F3 Gene

Christmas

Ursino

Fox

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cytochrome P450 4F3 (CYP4F3) catalyzes the inactivation of leukotriene B 4 by -oxidation in human neutrophils. To understand the regulation of CYP4F3 expression, we analyzed the CYP4F3 gene and cloned a novel isoform (CYP4F3B) that is expressed in fetal and adult liver, but not in neutrophils. The CYP4F3 gene contains 14 exons and 13 introns. The cDNAs for CYP4F3A (the neutrophil isoform) and CYP4F3B have identical coding regions, except that they contain exons 4 and 3, respectively. Both exons code for amino acids 66 -114 but share only 27% identity. When expressed in COS-7 cells, the K m of CYP4F3B was determined to be 26-fold higher than the K m of CYP4F3A using leukotriene B 4 as a substrate. 5-Rapid amplification of cDNA end studies reveal that the CYP4F3A and CYP4F3B transcripts have 5-termini derived from different parts of the gene and are initiated from distinct transcription start sites located 519 and 71 base pairs (bp), respectively, from the ATG initiation codon. A consensus TATA box is located 27 bp upstream of the CYP4F3B transcription start site, and a TATA box-like sequence is located 23 bp upstream of the CYP4F3A transcription start site. The data indicate that the tissue-specific expression of functionally distinct CYP4F3 isoforms is regulated by alternative promoter usage and mutually exclusive exon splicing. Leukotriene B 4 (LTB 4 )1 is synthesized from arachidonic acid by the sequential action of 5-lipoxygenase and leukotriene A 4 hydrolase enzymes in neutrophils, monocytes and macrophages (1). It is a potent chemoattractant for human neutrophils and also has chemotactic activity for monocytes (2-6). LTB 4 exerts this activity via a G protein-coupled receptor in target cells (7) and induces a cascade of cellular events that amplify the inflammatory response (8). The generation of LTB 4 is implicated in the pathogenesis of inflammatory disorders that involve prominent neutrophil infiltration of tissues (8, 9).Recently, it has been suggested that LTB 4 can also play an intracellular role in regulating transcription by functioning as a ligand for peroxisome proliferator-activated receptor ␣ (10). The bioactivity of LTB 4 is determined by the regulation and kinetic properties of the enzymes that control its synthesis and catabolism.LTB 4 is inactivated by -oxidation of its terminal carbon to yield 20-OH LTB 4 and 20-COOH LTB 4 (10, 11). The initial -hydroxylation is catalyzed by CYP4F3 (12-16), which by biochemical analysis has a restricted localization to neutrophils, and to a lesser extent monocytes (12, 17). The CYP4 family of enzymes catalyze the -hydroxylation of a large number of fatty acids and arachidonic acid derivatives (18). The CYP4F subfamily utilizes LTB 4 as a substrate. Two members of this subfamily have been identified in humans and are designated CYP4F3 (16, 19) and CYP4F2 (20). Studies of neutrophil microsomes or recombinant CYP4F3 have determined the specificity of CYP4F3 for LTB 4 (15, 21). CYP4F1, -4, -5, and -6 are designations given to rat enzymes (22, 23).The two human ...

show abstract

Section: Leukotriene B 4 (Ltb 4 )mentioning

confidence: 99%

Expression of the CYP4F3 Gene

Christmas

Ursino

Fox

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It is well known that low doses of neutrophil stimulants cause chemokinesis and chemotaxis, responses which however are progressively inhibited at higher stimulant concentrations (e.g. Schiffmann et al, 1975;Gallin et al, 1978;Smith & Walker, 1980;Palmer et al, 1980;Hoult & Nourshargh, 1985). These low doses of stimulants mobilize intracellular calcium (Korchak et al, 1984;Volpi et al, 1984;Rossi et al, 1985;Nourshargh, 1986) and are associated with chemotactic receptor up-regulation (Gallin, 1984), whereas higher doses are needed to elicit the respiratory burst and degranulation ofboth specific and azurophil granules (Lehmeyer et al, 1979;Korchak et al, 1984;Hoult & Nourshargh, 1985;Rossi et al, 1985) and phosphoinositide turnover with diacylglycerol formation (Dougherty et al, 1984;Rossi et al, 1985;Bradford & Rubin, 1985;but compare Volpi et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

Nourshargh

Hoult

1987

British J Pharmacology

View full text Add to dashboard Cite

The effects of two co‐carcinogenic phorbol esters (phorbol myristate acetate (PMA) and phorbol dibutyrate (PDBu)) and a synthetic diacylglycerol (OAG, 1‐oleoyl‐2‐acetyl‐glycerol), which all stimulate protein kinase C, were compared with two inactive phorbol compounds (4α‐phorbol and 4α‐phorbol didecanoate (4α‐PDD)) on three functional properties of stimulated human polymorphonuclear leukocytes (PMNs): release of granular enzymes lysozyme and β‐glucuronidase, chemokinesis, and changes in cytoplasmic free calcium [Ca2+]i. PMA, PDBu and the diacylglycerol, OAG, all caused a dose‐dependent and slow (max by 15 min) release of small amounts of lysozyme with much less β‐glucuronidase and no release of cytoplasmic lactate dehydrogenase. Release was unaffected by removal of extracellular Ca2+. PMA, PDBu and OAG inhibited random movement of the cells, did not cause chemokinesis and induced a slow reduction in the basal [Ca2+]i, as measured by the quin‐2 method. PMA, PDBu and OAG increased the capacity of five independently‐acting stimulants (N‐formyl‐Met‐Leu‐Phe, leukotriene B4, C5a des‐Arg, platelet activating factor and A23187) to cause release of lysozyme and β‐glucuronidase but strongly inhibited PMN chemokinesis induced by the same five agents and reduced the stimulant‐induced increases in [Ca2+]i. PMA was always more potent than PDBu and much more potent than OAG in eliciting these stimulatory or inhibitory effects on human PMNs. In all tests, 4α‐phorbol and 4α‐PDD were inactive. The results confirm that stimulation of the diacylglycerol/protein kinase C system in human PMN, either by active phorbol esters or the synthetic diacylglycerol, causes bidirectional effects on human PMN function. In particular, activation of the C‐kinase causes inhibition of stimulated neutrophil motility, whereas the secretory functions of the cells are enhanced.

show abstract

“…The 5-lipoxygenase pathway converts arachidonic acid to 5S-hydroperoxy-6,8,11,14 eicosatetraenoic acid which may be further transformed into leukotrienes (Samuelsson, 1983). Leukotriene B4 (LTB4) is a potent chemotactic agent (Ford-Hutchinson et al, 1980;Palmer et al, 1980;Nagy et al, 1982;Soter et al, 1983;Camp et al, 1983) and is a complete secretagogue in human neutrophils (PMN) (Showell et al, 1982). Leukotriene C4, D4 and E4 (LTC4, LTD4 and LTE4) comprise the activity previously known as slow reacting substance of anaphylaxis (SRS-A) (Murphy et al, 1979;Orning et al, 1980;Morris et al, 1980; Lewis et al, 1980;Piper, 1984).…”

Section: Introductionmentioning

confidence: 99%

The contractile activities of lipoxin A₄ and lipoxin B₄ for guinea‐pig airway tissues

Jacques

Spur

Crea

et al. 1988

British J Pharmacology

View full text Add to dashboard Cite

The isometric contractile activities of lipoxin A4 (LxA4) and lipoxin B4 (LxB4) were evaluated on guinea‐pig lung tissue over the concentration range, 10−8 to 10−5 m. LxA4 contracted guinea‐pig lung parenchymal strips; the concentration eliciting 50% maximum histamine response was 3 × 10−6 m. LxA4 did not contract tracheal spirals. The LxA4 dose‐response curve was parallel to that of leukotriene D4 (LTD4) with LxA4 being approximately 10,000 fold less potent than LTD4. The time course of the contraction elicited by LxA4 was similar to that of LTD4 and it was slow in onset and did not plateau for 20 min. Pre‐incubation of parenchymal strips with leukotriene receptor antagonists at a concentration of 1 × 10−6 m to 3 × 10−5 m FPL 55712 or 3 × 10−5 m L 649923 inhibited LxA4 activity. Pre‐incubation of tissues with 1 × 10−5 m L 651392, a 5‐lipoxygenase inhibitor, or 1 × 10−5 m indomethacin, a cyclo‐oxygenase inhibitor, did not affect the contractile activity of LxA4. LxB4 did not constrict parenchymal strips or tracheal spirals.

show abstract

Chemokinetic activity of arachidonic acid lipoxygenase products on leuocyctes of different species

Cited by 398 publications

References 12 publications

Expression of the CYP4F3 Gene

Expression of the CYP4F3 Gene

Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

The contractile activities of lipoxin A₄ and lipoxin B₄ for guinea‐pig airway tissues

Contact Info

Product

Resources

About

Chemokinetic activity of arachidonic acid lipoxygenase products on leuocyctes of different species

Cited by 398 publications

References 12 publications

Expression of the CYP4F3 Gene

Expression of the CYP4F3 Gene

Divergent effects of co‐carcinogenic phorbol esters and a synthetic diacylglycerol on human neutrophil chemokinesis and granular enzyme secretion

The contractile activities of lipoxin A4 and lipoxin B4 for guinea‐pig airway tissues

Contact Info

Product

Resources

About

The contractile activities of lipoxin A₄ and lipoxin B₄ for guinea‐pig airway tissues