Neutrophils and eosinophils infiltrate the airways in association with the allergen‐induced late phase asthmatic reaction. Mobilization of these cells takes place via lipid‐like and protein‐like chemotactic factors. In this study platelet‐activating factor (PAF), leukotriene B4 (LTB4), zymosan‐activated serum (ZAS) and N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) were used as illustrative examples of both groups. Chemotaxis was studied in human neutrophils and eosinophils. The inhibitory effects of nedocromil sodium and sodium cromoglycate were evaluated. All chemotactic factors tested attracted neutrophils with the following rank order of activity: ZAS > PAF ≡ FMLP ≡ LTB4. Eosinophils were only mobilized by PAF, LTB4 and ZAS with the following rank order of activity: ZAS > PAF > LTB4. Nedocromil sodium and sodium cromoglycate were equally active as the PAF antagonist BN 52021 in inhibiting the PAF‐induced chemotaxis of neutrophils (IC50 & 10−8 m). Both drugs were also equally active in inhibiting the chemotaxis of neutrophils induced by ZAS (IC50 ≅ 10−7−10−6 m), FMLP(IC50 ≅ 10−7 m) and LTB4 (IC50 ≅ 10−6 m). Nedocromil sodium significantly inhibited the chemotaxis of eosinophils induced by PAF (IC50 ≅ 10−6 m) and LTB4 (IC50 ≅ 10−7 m). The inhibitory potency of BN 52021 was similar to that of nedocromil sodium on the PAF‐induced chemotaxis of eosinophils. Sodium cromoglycate was incapable of eliciting significant inhibition of these chemotactic responses. However, sodium cromoglycate significantly inhibited the chemotaxis of eosinophils induced by ZAS (IC50 ≅ 10−7 m), whereas nedocromil sodium was ineffective.

Human granulocytes isolated from peripheral blood have been described to synthesize both LTB4 and LTC4 from arachidonic acid. We have observed that the amount of LTC4 produced by human granulocyte preparations is strongly dependent on the relative amount of eosmophils. To investigate a possibly significant difference in leukotriene synthesis of the eosinophilic and neutrophilic granulocytes, we developed a purification method to isolate both cell types from granulocytes obtained from the blood of healthy donors. Leukotrlenes were generated by incubation of the purified cells with arachidonic acid, calcium lonophore A23187, calcium-chlonde and reduced glutatbione. Surprisingly, eosinophils were found to produce almost exclusively the spasmogenic LTC4. In contrast, neutropbils produce almost exclusively the chemotactic LT&, its w-hydroxylated metabolite 20-hydroxy-LTB4 and two nonenzymically formed LTB4 isomers. Leukotnene Granulocyte Eosmophil

In allergic asthma eosinophils infiltrate into the lung after allergen challenge. The mechanism of this cellular infiltration is not fully understood. L-Selectin is involved in leucocyte-endothelial cell recognition and participates in homing of leucocytes into sites of inflammation. To find indications for a role of L-Selectin in the migration of eosinophils to the bronchoalveolar space we measured L-Selectin expression on eosinophils in peripheral blood and bronchoalveolar lavage fluid (BAL) 4 hr after the early allergic reaction after allergen challenge. Nine patients with allergic asthma participated in the study. An eosinophil specific high depolarization signal enabled us to measure L-Selectin expression on eosinophils in a FACS analysis without isolation of these cells. Eosinophils recovered from BAL showed a strong decrease of L-Selectin expression compared to blood eosinophils. This decrease in L-Selectin expression can be induced in vitro by activation of eosinophils with PMA or FMLP whereas priming of eosinophils during several hours with GM-CSF did not influence L-Selectin expression. Our results are a first indication that L-Selectin may play a role during homing of eosinophils in the lung in asthma after allergen challenge. Moreover, the low expression of L-Selectin on eosinophils in the lung is a further indication that these cells exhibit an activated phenotype.

No abstract