The LPS-induced neutrophil recruitment into rat air pouches is mediated by TNFα: likely macrophage origin

The role of resident cells during the lipopolysaccharide (LPS)-induced neutrophil recruitment into rat air pouches was investigated. In this model, LPS (Escherichia coli, O55: B5 strain; 2–2000 ng) induced a dose– and time-dependent neutrophil recruitment accompanied by the generation of a tumour necrosis factor-α (TNFα)-like activity. Dexamethasone (0.05–5 mug) and cycloheximide (6 ng), injected 2 h before LPS into the pouches, inhibited the neutrophil recruitment and the generation of the TNFα-like activity, while the H1-receptor antagonist mepyramine (1 and 4 mg/kg, i.p., 0.5 h before LPS) and the PAF-receptor antagonist WEB 2170 (0.05 and 1 mg/kg, i.p., 0.5 h before LPS) had no effect. Purified alveolar macrophages (AM) were used to replenish the pouches of cycloheximide-treated recipient rats. AM provided by PBS-treated animals led to the recovery of the LPS-induced neutrophil recruitment and of the TNFα-like formation contrasting with those from cycloheximide-treated animals (1 mg/kg, i.p.). When delivered in situ, liposome-encapsulated clodronate, a macrophage depletor, significantly impaired both the LPSinduced neutrophil recruitment and the TNFα-like activity. An anti-murine TNFα polyclonal antibody (0.5 h before LPS) was also effective. These results emphasize the pivotal role of macrophages for LPS-induced neutrophil recruitment via the formation of TNFα

Thromboxane A2 Accounts for Bronchoconstriction but not for Platelet Sequestration and Microvascular Albumin Exchanges Induced by fMLP in the Guinea Pig Lung

ABSTRACT ABBREVIATIONS: BC, bronchoconstriction; TX, thromboxane; fMLP, N-formyl-L-methionyl-L-leucyl-L-phenylalanine; PMN, polymorphonuclear neutrophils; technitium; '11ln, 111indium; 1311 131iodine; PAP, platelet-rich plasma; MDA, malondialdehyde; ABC, erythrocyte; Aev, extravascular albumin; PL, platelet; PG, prostaglandin; DMSO, dimethyl sulfoxide; U 46619, 1 5(S)-hydroxy-1 1 ,9-(epoxymethano)prosta-5Z,13E-dienoic acid; 1 2-HETE, 1 2-hydroxyeicosatetraenoic acid; 1 7-HHT, heptadecatnenoic acid