Neutrophil airway influx by platelet-activating factor in asthma: role of adhesion molecules and LTB4 expression

Platelet-activating factor (PAF)-induced neutrophil lung sequestration may require cell surface adhesion molecules (macrophage‐1 antigen (MAC‐1) and lymphocyte function-associated antigen‐1 (LFA‐1)). In this randomised, double-blinded, crossover study, theneutrophil kinetics after PAF and Lyso-PAF (L‐PAF) airway challenge were investigated in nine mild-intermittent asthmatics. Neutrophils were measured in peripheral blood (PB) before and at 5, 15, 45 and 240 min after bronchoprovocation, and in induced sputum before and at 240 min after challenge. MAC‐1 and LFA‐1 expression were assessed by immunocytochemistry, and leukotriene B4 (LTB4) was measured by enzyme-immunoassay in induced-sputum supernatants. Compared with baseline, neutrophils in PB decreased 5 min after PAF, while at 240 min neutrophils in induced sputum increased. Compared with baseline and L‐PAF, PAF decreased the percentages of MAC‐1‐ and LFA‐1‐positive neutrophils in PB at 5 min, but increased the percentages of MAC‐1 and LFA‐1 in neutrophil-induced sputum. Moreover, compared with baseline and L‐PAF, PAF-induced sputum revealed higher LTB4 levels, a finding that correlated with the elevated number of neutrophils in induced sputum. These findings suggest that macrophage‐1 antigen and lymphocyte function-associated antigen‐1 are involved in platelet-activating factor-induced neutrophil lung traffic, and that this process is modulated by enhanced leukotriene B4 release within the airways.

[1]  P. Ward,et al.  Neutrophil Adhesion to Human Endothelial Cells is Induced by the Membrane Attack Complex: The Roles of P-Selectin and Platelet Activating Factor , 2004, Inflammation.

[2]  W. MacNee,et al.  Potential role of IL‐8, platelet‐activating factor and TNF‐α in the sequestration of neutrophils in the lung: effects on neutrophil deformability, adhesion receptor expression, and chemotaxis , 2002, European journal of immunology.

[3]  J. Barberà,et al.  Pulmonary Gas Exchange and Sputum Cellular Responses to Inhaled Leukotriene D4 in Asthma , 2001 .

[4]  P. Gibson,et al.  Heterogeneity of airway inflammation in persistent asthma : evidence of neutrophilic inflammation and increased sputum interleukin-8. , 2001, Chest.

[5]  G. Bonsignore,et al.  15(S)-HETE modulates LTB(4) production and neutrophil chemotaxis in chronic bronchitis. , 2000, American journal of physiology. Cell physiology.

[6]  M. Matthay,et al.  Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. , 2000, American journal of respiratory and critical care medicine.

[7]  P. Gibson,et al.  Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. , 2000, American journal of respiratory and critical care medicine.

[8]  S. Tasaka,et al.  CD11/CD18-dependent and -independent neutrophil emigration in the lungs: how do neutrophils know which route to take? , 2000, American journal of respiratory cell and molecular biology.

[9]  Z. Ding,et al.  Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. , 1999, Journal of immunology.

[10]  K. Chung,et al.  Neutrophilic inflammation in severe persistent asthma. , 1999, American journal of respiratory and critical care medicine.

[11]  P. Gaehtgens,et al.  A role for β2 integrins (CD11/CD18) in the regulation of cytokine gene expression of polymorphonuclear neutrophils during the inflammatory response , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  R. Stockley,et al.  The interrelationship of sputum inflammatory markers in patients with chronic bronchitis. , 1999, American journal of respiratory and critical care medicine.

[13]  G. Nash,et al.  Adhesion-dependent release of elastase from human neutrophils in a novel, flow-based model: specificity of different chemotactic agents. , 1998, Blood.

[14]  J. Wood,et al.  Platelet activating factor (PAF) increases leukocyte adhesion but does not alter vessel diameter in the rat mesenteric microcirculation. , 1998, Microvascular research.

[15]  X. Busquets,et al.  Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[16]  Yuan Yuan,et al.  Neutrophil-dependent augmentation of PAF-induced vasoconstriction and albumin flux in coronary arterioles. , 1998, American journal of physiology. Heart and circulatory physiology.

[17]  J. D. de Monchy,et al.  Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro. , 1998, The European respiratory journal.

[18]  W. Busse.  The role and contribution of leukotrienes in asthma. , 1998, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[19]  Y. Masuho,et al.  Synergistic effect of type II phospholipase A2 and platelet-activating factor on Mac-1 surface expression and exocytosis of gelatinase granules in human neutrophils: evidence for the 5-lipoxygenase-dependent mechanism. , 1998, Journal of immunology.

[20]  J. Barberà,et al.  The effects of 5-lipoxygenase inhibition by zileuton on platelet-activating-factor-induced pulmonary abnormalities in mild asthma. , 1998, American journal of respiratory and critical care medicine.

[21]  K. Shindo,et al.  Platelet-activating factor increases leukotriene B4 release in stimulated alveolar macrophages from asthmatic patients. , 1998, The European respiratory journal.

[22]  E. Bel,et al.  CD11b and L‐selectin expression on eosinophils and neutrophils in blood and induced sputum of patients with asthma compared with normal subjects , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[23]  F. Saulnier,et al.  Bronchial neutrophilia in patients with noninfectious status asthmaticus. , 1998, American journal of respiratory and critical care medicine.

[24]  K. Shindo,et al.  Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by platelet activating factor. , 1997, Thorax.

[25]  S. Wenzel,et al.  Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. , 1997, American journal of respiratory and critical care medicine.

[26]  P. Sterk,et al.  Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma. , 1996, The European respiratory journal.

[27]  J. Barberà,et al.  Salbutamol reduces pulmonary neutrophil sequestration of platelet-activating factor in humans. , 1996, American journal of respiratory and critical care medicine.

[28]  F. Hargreave,et al.  Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. , 1996, American journal of respiratory and critical care medicine.

[29]  G. Trinchieri,et al.  Lipopolysaccharide-induced interleukin-8 gene expression in human granulocytes: transcriptional inhibition by interferon-gamma. , 1995, The Biochemical journal.

[30]  Kwang Woo Kim,et al.  Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. , 1995, The Journal of allergy and clinical immunology.

[31]  J. Wilson.  Leukotriene B 4 , 1995 .

[32]  J. Barberà,et al.  Inhaled platelet-activating factor worsens gas exchange in mild asthma. , 1994, American journal of respiratory and critical care medicine.

[33]  G. Gleich,et al.  Sudden-onset fatal asthma. , 1994, Mayo Clinic proceedings.

[34]  J. Barberà,et al.  Platelet-activating factor causes ventilation-perfusion mismatch in humans. , 1994, The Journal of clinical investigation.

[35]  C E Reed,et al.  Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? , 1993, The American review of respiratory disease.

[36]  K. Chung,et al.  Role of inflammatory mediators in asthma. , 1992, British medical bulletin.

[37]  S. Albelda.  Endothelial and epithelial cell adhesion molecules. , 1991, American journal of respiratory cell and molecular biology.

[38]  A. Wardlaw,et al.  Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness. , 1990, The American review of respiratory disease.

[39]  M J Smith,et al.  Leukotriene B4. , 1981, General pharmacology.