+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

British Journal of Pharmacology 98(1): 61-70

1. N-formyl-methionyl-leucyl-phenylalanine (FMLP), when administered by aerosol to guinea-pigs, 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. Non-degranulated eosinophils were observed in the lungs and a few platelet micro-aggregates in the pulmonary microvasculature. 3. No significant accumulation of 131I-labelled albumin, 111In-labelled neutrophils or 111Inlabelled 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 sub-maximal 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. 6. The dual cyclo-oxygenase/lipoxygenase inhibitor compound BW755C suppressed the BC induced by an aerosol of FMLP at all the concentrations used, whereas the histamine H1-antagonist mepyramine was inactive. 7. Leukocyte depletion with vinblastine failed to reduce BC induced by intravenous or an aerosol of FMLP. 8. Our studies indicate that: (a) FMLP administered by aerosol induces dose-dependent BC followed by desensitization, indicating that local mechanisms account for BC; (b) BC induced by i.v. FMLP, but not by its inhalation, is accompanied by albumin extravasation and neutrophil sequestration in the lungs; (c) BC by either i.v. or an aerosol of FMLP is not due to neutrophil activation; (d) inhalation of FMLP induces BC accompanied by accumulation of activated alveolar macrophages, non-degranulated eosinophils and a few platelet microaggregates in the lung; (e) both cyclo-oxygenase and lipoxygenase metabolites are involved in the BC induced by an aerosol of FMLP.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 039225651

Download citation: RISBibTeXText

PMID: 2508985

DOI: 10.1111/j.1476-5381.1989.tb16863.x

Related references

The arachidonate cascade and alveolar macrophages but not neutrophils mediate bronchoconstriction by fmlp in guinea pigs. British Journal of Pharmacology 96(Suppl.): 78P, 1989

Release of PAF-acether and eicosanoids from guinea-pig alveolar macrophages by FMLP: effect of cyclo-oxygenase and lipoxygenase inhibition. European Journal of Pharmacology 164(3): 539-546, 1989

Ovalbumin sensitization of guinea-pigs reduces fMLP-induced calcium signal in alveolar macrophages. Life Sciences 69(14): 1597-1607, 2001

Desensitization to PAF-induced bronchoconstriction and to activation of alveolar macrophages by repeated inhalations of PAF in the guinea pig. Biochemical and Biophysical Research Communications 131(1): 42-49, 1985

The effects of PAF-acether and FMLP on eicosanoid production in guinea pig alveolar macrophages. Agents and Actions 26(1-2): 115-116, 1989

Enhancement of the phospholipase A2activity in fMLP-treated guinea-pig alveolar macrophages. Inflammation Research 26(1-2): 256-257, 1989

Enhancement of the phospholipase A2 activity in fMLP-treated guinea-pig alveolar macrophages. Agents and Actions 26(1-2): 256-257, 1989

The superoxide generation of alveolar macrophages and circulating neutrophils at various stages during the development of bleomycin induced pulmonary fibrosis in the guinea pig. Clinical Research 40(2): 411A, 1992

Neutrophils mediate the increased intestinal vascular permeability induced by luminal perfusion with n formylmethionylleucylphenylalanine fmlp. Gastroenterology 92(5 Part 2): 1413, 1987

Thromboxane A2 accounts for bronchoconstriction but not for platelet sequestration and microvascular albumin exchanges induced by fMLP in the guinea pig lung. Journal of Pharmacology and Experimental Therapeutics 260(2): 832-840, 1992

Role of eicosanoids in hyperpnea induced bronchoconstriction hib and bronchovascular hyperpermeability hibvh in guinea pigs. American Review of Respiratory Disease 143(4 Part 2): A539, 1991

Comparison of the effects of selective PDE4 inhibitors on fMLP-induced O2- production in neutrophils and macrophages. Inflammation Research 50(Suppl. 3): S200, 2001

Alveolar macrophages and neutrophils are the primary reservoirs for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion. Infection and Immunity 82(10): 4325-4336, 2014

Signal transduction in human alveolar macrophages: diminished chemotactic response to FMLP correlates with a diminished density of Gi proteins and FMLP receptors. American Journal of Respiratory Cell and Molecular Biology 5(1): 87-92, 1991

Tachykinins mediate hypocapnia-induced bronchoconstriction in guinea pigs. Journal of Applied Physiology 67(6): 2454-2460, 1989