Biological and cellular responses to grass pollen in sensitive patients.

Using a noninvasive skin chamber technique, we studied the in vivo development of anaphylactic reactions in 8 pollen-sensitive patients suffering from seasonal allergic rhinitis/conjunctivitis/asthma and showing positive cutaneous reactions after intradermal allergen challenge. As agonists, histamine and pollen were introduced into the skin chambers and left in contact with superficial dermis during 6 h. The release of mediators (histamine and prostaglandin [PG] D2) and the modifications in protein diffusion occurring during the immediate (30 min) and the late (6 and 24 h) cutaneous reaction phases were quantitatively analyzed.

Biosynthesis of paf-acether factor-acether by human skin fibroblasts in vitro.

The synthesis and release of paf-acether by fibroblasts from normal human skin was investigated in vitro. When fibroblasts in suspension (1 X 10(6) cells) were stimulated with 2 microM Ca1+ ionophore A23187 (Io), they synthesized a material that aggregated aspirin-treated washed rabbit platelets and was identified as paf because 1) the platelet aggregation it induced was inhibited by BN 52021, an antagonist of paf putative receptors; 2) the factor was inactivated by phospholipase A2 but was insensitive to lipase from Rhizopus arrhizus; 3) it exhibited the same retention time as synthetic paf during standard and reverse phase HPLC elution. Paf production by fibroblasts occurred as soon as the first min of Io stimulation (287 +/- 92 pg/1 X 10(6) cells), reached a maximum at 5 min (369 +/- 85 pg/1 X 10(6) cells) and decreased thereafter.

[Synthesis of paf-acether by E. coli K12].

Paf-acether (platelet-activating factor) is one of the most potent mediator of inflammation released from and acting on most cells that participate in inflammatory diseases. Its molecular structure is 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. Two metabolic steps are involved in its biosynthesis: the action of a phospholipase A2 on choline-containing membrane alkyl-ether lipids results in the production of lyso paf-acether and acetylation of the lyso compound by an acetyltransferase yields the biologically active molecule.