Increased generation of the arachidonic metabolites LTB4 and 5-HETE by human alveolar macrophages in patients with asthma: effect in vitro of nedocromil sodium.
Alveolar macrophages (AM) are the principal resident phagocytes in the human lung, and play a major role in local defence against environmental agents. It is now known that during asthma these cells take part in the amplification of the inflammatory mechanism. It has been demonstrated in vitro that they can be activated to generate leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE), mediators with potent pharmacological properties. These two arachidonic metabolites were identified and quantified by reversed phase high performance liquid chromatography (HPLC) performed in cell suspensions, and in cell free supernatants. AM from asthmatics, after stimulation by the calcium ionophore A23187 or opsonized zymosan, released significantly (p less than 0.05) more LTB4 than those from healthy subjects. The increase in LTB4 release could be evidence for in vivo activation. On the other hand, the levels of 5-HETE in the AM from asthmatics were significantly (p less than 0.03) higher than those in cells from healthy subjects. This intracellular increase could be correlated with a greater migratory ability of these inflammatory macrophages, as observed for eosinophils. The clinical efficacy of nedocromil sodium may be partly related to the decreases in LTB4 releasability and intracellular 5-HETE levels observed only in AM from asthmatic patients.
Damon
M
M
INSERM U.58, Montpellier, France.
Chavis
C
C
Daures
J P
JP
Crastes de Paulet
A
A
Michel
F B
FB
Godard
P
P
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017835:Nedocromil; D011650:Pulmonary Alveoli; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D015054:Zymosan / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D015363:Quinolones; D017835:Nedocromil; D007975:Leukotriene B4; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D015054:Zymosan