Sources of Arachidonic Acid in Human Lung Macrophages.

The aim of this study was to define the lipid pools in which arachidonic acid (AA) is stored and from which it is released upon activation of human lung macrophages (HLM). HLM incorporate exogenous AA into neutral lipids (triglycerides) and into the major phospholipid classes. HLM also possess an AA pool not previously reported in other human cells. Initial characterization of this arachidonate-containing lipid suggests it is bis-(monoacylglyceryl)-phosphate (BMP). HLM labeled with 3H-AA for 24 h released 7.6 and 15.5% of their total radioactivity in the supernatant after 30 min of stimulation with TPA (10--6M) and the Ca2+ ionophore A23187 (10--6M), respectively. AA was released from all phospholipid pools, mostly from phosphatidylethanolamine and phosphatidylcholine. In contrast, the amount of radioactivity in the triglyceride pool rapidly increased in activated HLM. These data demonstrate the existence of a novel AA-containing phospholipid in HLM, tentatively identified as BMP, and that, although these cells contain large stores of AA in triglycerides, the only sources of AA available for eicosanoid synthesis in stimulated HLM are phospholipids.

Modulation of Human Lung Mast Cell Function by the c-kit Receptor Ligand.

The gene product of the steel locus is a growth factor for mast cells and a ligand for the c-kit proto-oncogene receptor, a member of the tyrosine kinase receptor class of oncogenes. We studied the effect of recombinant human c-kit receptor ligand stem cell factor (rhSCF) on the release of preformed (histamine) and de novo synthesized mediators [prostaglandin D2 (PGD2) and peptide leukotriene C4 (LTC4)] from mast cells purified from human lung parenchyma (HLMC). rhSCF (0.01-10 ng/ml) concentration-dependently induced histamine release from HLMC. rhSCF also induced the de novo synthesis of PGD2, whereas it did not induce the release of LTC4. The release of mediators from HLMC caused by rhSCF was extremely rapid, and was Ca2+- and temperature-dependent.

8-Methoxypsoralen and long-wave ultraviolet A inhibit the release of proinflammatory mediators and cytokines from human Fc epsilon RI+ cells: an in vitro study.

The in vitro effects of 8-MOP (concentrations of 20, 100 and 500 ng/ml) alone or in combination with UVA on mediator release from human basophils and skin mast cells (HSMC), activated with immunological and non-immunological stimuli, were investigated. With respect to basophils activated with anti-IgE serum, the results of this study show that: (i) 8-MOP alone inhibits histamine, LTC(4), IL-4 and IL-13 release concentration dependently with a maximal effect at 500 ng/ml (a concentration not reached in vivo); and (ii) UVA irradiation (5 J/cm(2)), after 8-MOP incubation, enhances this inhibitory effect on all released mediators, but for IL-4 and IL-13 the percentage inhibition is also significant for the 8-MOP concentrations (20-100 ng/ml) employed in vivo during PUVA treatment. Moreover, histamine release from basophils activated with non-immunological stimuli (FMLP and A23187) is inhibited by 8-MOP, alone or in combination with UVA. With respect to the HSMC activated with anti-IgE serum, the results show that: (i) 8-MOP alone reduces histamine release concentration dependently; and (ii) this inhibitory effect is enhanced by UVA irradiation (5 J/cm(2)). Histamine release from HSMC activated with A23187 is not modified either by 8-MOP alone or by 8-MOP plus UVA.

Mastocytosis presenting as cardiac emergency.

Mastocytosis is characterised by clonal proliferation of mast cells in the skin and in various internal organs, and by symptoms related to an acute release of mast cell-derived mediators. In 20-30 % of patients, mastocytosis occurs without the typical skin lesions of urticaria pigmentosa that are usually the first clinical sign of the disease. In these patients, anaphylaxis is often the presenting sign of the disease. We report three cases in which a cardiac emergency (cardiac arrest or ventricular fibrillation) was the first clinical manifestation of anaphylaxis associated with systemic mastocytosis. All patients were men, none of them had previous episodes of anaphylaxis or other mediator-related symptoms, and none had major pre-existing cardiovascular condition. An eliciting factor was identified in one case (a wasp sting), but one was found in the other two. Elevation of the serum tryptase suggested a mastocytosis, which was confirmed by bone marrow biopsy. This case series demonstrates that cardiovascular emergencies may be presenting signs of mastocytosis, and that elevation of serum tryptase after an acute cardiac event, if confirmed under basal conditions, may be useful for diagnosing this disease.