Histamine-potentiating activity in rat anaphylactic pleural fluid: role of serotonin

The identity of the histamine-potentiating activity detected in the rat anaphylactic pleural washing was investigated. Wistar rats of both sexes, weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of ovalbumin and Al(OH)3 14 days before allergen challenge. In sensitized rats, intrapleural (ipl) injection of ovalbumin (l2 mug/cavity) caused an intense protein exudation. A single ipl administration of compound 48/80 (l2 mug/cavity) exhausted the resident mast cell population and turned the pleural cavity hyporeactive to the allergen challenge performed 5 days later. Allergen-induced exudation occurred in parallel to a dramatic decrease in the amount of cell-stored histamine (from 9.6 ñ 1.4 (N = 8) to 1.3 ñ 0.1 (N = 6) mug/cavity, P<0.001) in the pleural fluid within 10 min. The anaphylactic cell-free pleural washing obtained at this time, as well as histamine at a concentration equivalent to that stored in pleural mast cells (10 mug/cavity), did not induce pleural exudation when injected into normal rats. In contrast the combined administration of histamine and anaphylactic pleural washing led to remarkable pleural exudation, comparable to that obtained with a high dose of histamine (200 mug/cavity) alone. It is noteworthy that the anaphylactic washing from compound 48/80 pretreated rats failed to synergize with histamine. Also, synergism was not reproduced when recipient rats were pretreated with methysergide (50 mug/cavity). Consistently, serotonin (5 mug/cavity) acted synergistically with histamine (1O mug/cavity), producing a greater exudative response than observed with the sum of the effects of each vasoactive amine alone. The results indicate that serotonin accounts for the histamine-potentiating activity noted in the anaphylactic pleural washing, confirming that the synergistic interaction between these vasoactive amines plays a critical role in the rat allergic pleurisy.

Kinetics of pleural exudation and cellular alterations induced by antigen in actively sensitized rats

This study was undertaken to characteize the different phases of the allergic pleurisy induced by ovalbumin in actively sinsitized rats. The reaction was triggered by the intrathoracic injection of ovalbumin (12 microng/cavity) into animals sensitized 14 days before. The challenge caused, at 30 mjin, a drastic mast cell degranulation and exudation which peaked within 4h. At this time, an intense pleural leucocyte recruitment also occurred, accounted for by an increase in the mononuclear cell counts and by a predominant influyx of neutrophils. After 24h, the mast cell counts stated to reover, accompanied by a long-lasting (96 h) accumaltion of pleural eosinophils. Forty-eight hour later, the exudation and neutrophils were at basal levels, whereas mast cell counts increased progressively to reach control values at 120 h. This study describes the time course of the exudatory and cellular alterations observed during pleural inflammation induced by low antigen concentrations