Alveolar macrophages and eicosanoids but not neutrophils, mediate bronchoconstriction induced by FMLP in the guinea‐pig

Abstract

1 N-formyl-methionyl-leucyl-phenylalanine (FMLP), when administered by aerosol to guineapigs, induced a dose-dependent bronchoconstriction (BC) with no overt effect on platelet and leukocyte blood counts. Repeated administration of FMLP by aerosol was followed by desensitization. 2 Electron microscopy studies showed that administration of FMLP by aerosol is accompanied by alveolar macrophage activation, accumulation and aggregation in the alveolar lumens. Nondegranulated eosinophils were observed in the lungs and a few platelet micro-aggregates in the pulmonary microvasculature.3 No significant accumulation of 13'I-labelled albumin, 1"'In-labelled neutrophils or "'Inlabelled platelets was detected in the lungs after the administration of FMLP by aerosol, whereas the intravenous administration was accompanied by an increase of extravascular albumin and significant neutrophil sequestration in the lungs. 4 Aspirin administered intravenously or by aerosol reduced significantly the BC induced by an aerosol of FMLP. By contrast, intravenous indomethacin reduced only BC induced by the submaximal dose of FMLP as an aerosol whereas, when administered by inhalation, it inhibited BC induced by FMLP administered either intravenously or by aerosol at all the concentrations tested. 5 FMLP induced a dose-dependent contraction of the guinea-pig trachea, which was not inhibited by indomethacin.

Comparison of the effects of intra‐arterial and aerosol administration of endothelin‐1 (ET‐1) in the guinea‐pig isolated lung

“…This pretreatment, however, significantly reduced the release of TxB2 induced by aerosolized arachidonic acid, and has been reported to suppress the bronchoconstriction induced by aerosolized FMLP in the guinea-pig. Indeed, Boukili et al (1989) have demonstrated that indomethacin administered by aerosol to anaesthetized guinea-pigs significantly reduced the bronchoconstriction induced by both intravenous and aerosol administration of FMLP and abrogated that evoked by intravenous injection of arachidonic acid, suggesting a predominant cyclooxygenase-dependent component in these experiments. Under our experimental conditions, aerosol administration of indomethacin (100mgml-1, for 20min) suppressed the in vivo bronchoconstriction evoked by intravenous injection of arachidonic acid (0.5mgkg-'; Pons et al, unpublished results). Interestingly, although pretreatment of the animals or addition of indomethacin to the perfusion medium significantly decreased TxB2 formation induced in vitro by arachidonic acid by more than 65%, minimal effect of this drug on the increase in PIP was noted.…”

Pharmacological differentiation by pertussis toxin of the in vivo acute responses to fMLP and PAF in guinea‐pig lungs

“…We demonstrate that different pathways are involved with the transduction of the signals generated by these agonists. The intravenous injection of fMLP or of PAF to guinea-pigs induced bronchoconstriction, a prolonged pulmonary sequestration of leucocytes and a transient sequestration of platelets, long lasting leucopenia and thrombocytopenia, increased capillary exchanges and a decrease of the lung blood volume, indicating pulmonary vasoconstric-40 50 60 tion Boukili et al, 1989). Imaizumi et al (1992) demonstrated that bronchoconstriction by intravenous fMLP in guinea-pigs is prevented by pertussis toxin, as is the Lt on PAF-induced lung case here for intra-tracheal fMLP (Kadiri et al, 1992).…”

Inhibition of neutrophil migration in mice by mouse formyl peptide receptors 1 and 2 dual agonist: indication of cross-desensitization in vivo

“…tion has previously been demonstrated only under in vitro conditions. Although fMLF-induced cross-desensitization in vitro has been well documented, [13][14][15][16][17] in most cases it has been reported that the administration of fMLF in vivo induces typical effects of chemoattractants on neutrophils, such as neutrophil infiltration into the airway induced by the inhalation of fMLF [22][23][24] and transient neutropenia induced by the intravenous administration of fMLF. 25,26 Among these studies, only Ley et al 25 reported the possibility of an inhibitory effect of fMLF on neutrophil migration towards chemoattractants.…”