Exposure of guinea‐pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 μg ml−1) induced a dose‐dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid.
Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range.
Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 μg ml−1).
PAF‐induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64–412, a selective PAF‐antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF.
Pulmonary airway eosinophil accumulation due to inhaled PAF (10 μg ml−1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21–132.
Pulmonary airway eosinophil accumulation due to inhaled PAF (10 μg ml−1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine.
Inhalation of ovalbumin by conscious, sensitized guinea pigs induced two phases of airway obstruction measured at 2 h (EAR) and at 17 h (LAR), respectively. In addition to causing airway obstruction, allergen challenge induced an accumulation in the bronchial lumen of eosinophil and neutrophil polymorphonuclear leukocytes at 17 h. Intraperitoneal injection of guinea pigs with a specific rabbit anti-guinea pig neutrophil serum 24 h before challenge reduced the number of circulating neutrophils by 94% and the airway neutrophilia after challenge by 90%, but it had no effect on the magnitude of either the EAR or the LAR. The observation that the LAR was not effected by neutropenia supports previous conclusions derived from experiments using the anti-allergic drugs, cromolyn sodium and nedocromil sodium, and the beta 2-adrenoceptor stimulant, albuterol, that, although there is a temporal relationship between neutrophil accumulation in the airways and the peak of the LAR, this polymorphonuclear leukocyte does not play a central role in the pathophysiologic processes that give rise to the late-phase response to guinea pig airways.
On the basis of previous studies on the structure-activity relationship of model polypeptide histamine liberators, a site within the Fc region of immunoglobulin E antibody molecules has been proposed as that responsible for the direct triggering of target mast cells after antigen challenge. Peptides comprising this region of the epsilon-chain have now been synthesized and shown to induce histamine release from normal rat peritoneal mast cells in a selective manner essentially similar to that mediated by anaphylactic antibody-antigen interaction.
Intraperitoneal injections of recombinant human granulocyte‐macrophage colony stimulating factor (rh‐GMCSF, 50 μg kg−1 daily) or interleukin‐3 (rh‐IL3, 50 μg kg−1 daily) for two days, induced an increase in the percentage of bone marrow and pulmonary airway eosinophils in the guinea‐pig. In addition, rh‐IL3‐treated animals exhibited an increase (21%) in blood neutrophils. Exposure of guinea‐pigs to an aerosol of platelet activating factor (PAF) gives rise to a selective pulmonary eosinophil accumulation, maximal at 48 h. The eosinophilic response to PAF was significantly enhanced in rh‐GMCSF‐treated guinea‐pigs but was suppressed in rh‐IL3‐treated animals.
The thoracic accumulation of neutrophils labelled with 111Indium-oxine in response to infusion of platelet activating factor (PAF, 18 ng/kg/min x 5 min, i.v.) was studied using an automated isotope monitoring system (AIMSplus) in anesthetized guinea-pigs. Loss of cell associated radioactivity in vitro was less than 1% over 4 hr. Labelled neutrophils maintained their functional capacity (oxidative response to the cell stimulants N-formyl-L-methionine-L-leucine-L-phenylalanine and phorbol myristate acetate) and greater than 95% viability (ethidium bromide/acridine orange stain) in vitro. Total thoracic radioactivity increased significantly from baseline in response to PAF with a slight tachyphylaxia in the neutrophil-accumulation after a repeat PAF infusion. The highest ratios of radiolabel (tissue/blood) were found in the spleen much greater than liver greater than lung.
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