Interference of a neutrophil recruitment inhibitory factor upon the accumulation of inflammatory cells and airway hyperreactivity in sensitized guinea‐pigs after intranasal antigen challenge

• Published in: British journal of pharmacology Vol. 108; no. 2; pp. 538 - 543
• Main Authors: Tavares‐Murta, B.M., Lefort, J., Cunha, F.Q., Ferreira, S.H., Vargaftig, B.B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.1993; Nature Publishing
• Subjects: Administration, Intranasal; Allergic diseases; Animals; Biological and medical sciences; Bronchial Hyperreactivity - drug therapy; Bronchoalveolar Lavage Fluid - cytology; cell migration; Guinea Pigs; Histamine Release - drug effects; hyperreactivity; Immunization; Immunopathology; Inflammation - drug therapy; Inflammation - pathology; Injections, Intravenous; intranasal antigen challenge; Intubation, Intratracheal; Leukocyte Migration-Inhibitory Factors - pharmacology; Lipopolysaccharides - administration & dosage; Lung - metabolism; Male; Medical sciences; Neutrophil recruitment inhibitory factor; Neutrophils - drug effects; Ovalbumin; Respiratory and ent allergic diseases; sensitized guinea‐pigs; Thromboxane B2 - metabolism; Cell factor; Immunopathology; Intravenous administration; Hyperreactivity; Pathophysiology; Respiratory disease; Cytokine; Inflammation; Biological activity; Asthma; Animal; Neutrophil; Mechanism of action; Macrophage
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb12837.x

1 A neutrophil recruitment inhibitory factor (NRIF) recovered from the crude supernatant of lipopolysaccharide (LPS)‐stimulated macrophages inhibited neutrophil migration following both intratracheal and intravenous administration of LPS, but did not alter the pattern of leukopenia/leucocytosis induced by intravenous LPS. 2 The correlation between airway infiltration by inflammatory cells and hyperreactivity in lungs from actively sensitized and challenged guinea‐pigs was investigated by use of NRIF. 3 Increased eosinophil counts were found in the bronchoalveolar lavage fluid from guinea‐pigs sensitized with 10 μg ovalbumin and challenged at day 14 by the intranasal administration of the antigen. The increase was evident 5 h after challenge and persisted at 24 h. Neutrophil numbers were also increased at this time. Pretreatment with NRIF suppressed the leucocyte increase in the bronchoalveolar lavage fluid. 4 Bronchoconstriction and histamine release induced by 3 ng PAF injected into the isolated lungs were increased in challenged guinea‐pigs as compared to sensitized but unchallenged controls. Pretreatment of the animals with NRIF did not interfere with this response, but significantly reduced the bronchoconstriction induced by ovalbumin injection. 5 Even though the increased number of inflammatory cells in bronchoalveolar lavage and airway hyperresponsiveness were concomitant, NRIF inhibited cellular infiltration but failed to alter airway hyperreactivity to PAF, demonstrating that these events may occur independently. Conversely, the inhibition of antigen‐induced bronchoconstriction by NRIF suggests that this response is dependent upon the emigration of granulocytes.