Increased generation of the arachidonic metabolites LTB and 5-HETE by human alveolar macrophages

Increased generation of the arachidonic metabolites J.:[B 4 and 5-HETE by human alveolar macrophages in patients with asthma: effect in vitro of nedocromil sodium. M. Damon, C. Chavis, J.P. Daures, A. Crastes de Paulet, F.B. Miche/, Ph. Godard. * INSERM U.58, 60 rue de Navacelles, •• Departement de !'Information Mcdicale, Hopi· tal l..apcyronie, *** Clinique des Maladies Respiratoires, avenue du Major Flandre, 34090 Montpellier, France. ABSTRACT: Alveolar m.acrophages (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 'l'ilro that they can be activated to generate Jeukotriene B 4 (LTB4) and 5-bydroxyelcosatetraenoic acid (5-HETE), mediators with potent pharmacological properties. These two aracWdonlc metabolltes were identified and quantified by reversed phase high performance Uquld 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<0.05) more LTB 4 than those from healthy subjects. The Increase In LTB 4 release could be evidence for in vivo activation. On the other band, the levels of 5-HETE in the AM from asthmatics were significantly (p<0.03) higher tha.n those In cells from healthy subjects. This Intracellular increase could be correlated with a greater migratory ability of these Inflammatory macrophages, as observed for eoslnophlls. The clinical efficacy of nedocromll sodium may be partly related to the decreases in LTB4 releasability and intracellular 5HETE levels observed only in AM from asthmatic patients. Correspondence: Dr M. Damon, INSERM U.58, 60 rue de Navacelles, 34090 Montpellier, France.