Therapeutic surfactants modulate the viability of eosinophils and induce inflammatory mediator release.
BACKGROUND
There is increasing interest in testing surfactant preparations for asthma therapy. Previously, Curosurf was demonstrated to increase inflammation in allergic asthmatics. So far, little is known about the immunomodulatory effects of therapeutic surfactants, in particular concerning the interaction of surfactant components with eosinophils as key effector cells of the allergic airway inflammation. The aim of the present study was to determine the effect of different therapeutic surfactants on cellular functions of eosinophils.


METHODS
Eosinophils were isolated from peripheral blood of atopic volunteers and incubated with the natural animal-derived surfactants Curosurf or Alveofact or the synthetic recombinant human surfactant Venticute at different concentrations for up to 42 h.


RESULTS
Curosurf and Venticute modulated the viability of eosinophils. While incubation with Curosurf increased the number of necrotic eosinophils after 1, 20 and 42 h, Venticute increased the number of apoptotic and necrotic cells after 1 h, but there were no differences compared with control cells at later time points. All surfactant preparations increased the levels of eosinophil cationic protein after 20 h and, in addition, Curosurf enhanced eosinophil cationic protein release after 42 h. The supernatant of eosinophils induced chemotaxis against autologous eosinophils, and the presence of Curosurf, but not Alveofact or Venticute, augmented the chemotactic effect. Chemotaxis was partly blocked by inhibition of eotaxin but not by inhibition of leukotrienes or platelet-activating factor.


CONCLUSIONS
Therapeutic surfactants differ in their effects on eosinophil viability and the accompanying release of inflammatory mediators and chemotactic signals. Proinflammatory effects were most pronounced for the natural surfactant Curosurf.
Erpenbeck
Veit J
VJ
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Fischer
Ina
I
Wiese
Kathrin
K
Schaumann
Frank
F
Schmiedl
Andreas
A
Nassenstein
Christina
C
Krug
Norbert
N
Hohlfeld
Jens M
JM
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000276:immunology; D016227:Benzoquinones / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D054413:Chemokine CCL11 / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D047150:Eosinophil Cationic Protein / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000276:immunology; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D010743:Phospholipids / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives
D016227:Benzoquinones; D001688:Biological Products; D054413:Chemokine CCL11; D007155:Immunologic Factors; D018836:Inflammation Mediators; D047029:Lactams, Macrocyclic; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C078272:SF-RI 1, bovine surfactant preparation; C521929:Venticute; D017828:Rifabutin; C020754:herbimycin; D047150:Eosinophil Cationic Protein; C068291:poractant alfa