GM-CSF Differentially Regulates Eosinophil and Neutrophil Adhesive Interactions with Vascular Endothelium in Vivo

• Main Authors: Nooshin Sheikh Bahaie, Savita P. Rao, Ahmad Massoud, P. Sriramarao
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2010-12-01
• Series: Iranian Journal of Allergy, Asthma and Immunology
• Subjects: Allergic Inflammation; Cytokines; Leukocyte Rolling; L-selectin
• Online Access: https://ijaai.tums.ac.ir/index.php/ijaai/article/view/346
• ISSN: 1735-1502; 1735-5249

Allergic airway inflammation is characterized by elaboration of cytokines and chemokines leading to recruitment of inflammatory leukocytes, predominantly eosinophils, to the airways. Granulocyte macrophage colony stimulating factor (GM-CSF) is generated in the lungs of human subjects with asthma in response to allergen challenge and is necessary for the development of allergen-induced bronchial eosinophilia in mice. The effect of GM-CSF on human eosinophil and neutrophil interactions with the vascular endothelium under conditions of blood flow was investigated in post-capillary venules of the rabbit mesentery by intravital microscopy. While GM-CSF significantly reduced the rolling fraction of neutrophils in vivo and induced consistent shedding of neutrophil L-selectin in vitro, its effect on eosinophil rolling was variable. Eosinophils from 57% of the donors demonstrated inhibition of rolling, while eosinophils from the remaining 43% of donors demonstrated no inhibition or increased rolling. The variable effect of GM-CSF on inhibition of eosinophil rolling was associated with variable shedding of L-selectin in vitro. In contrast to the differential effect of GM-CSF on neutrophils versus eosinophils, stimulation with phorbol myristate acetate demonstrated a similar degree of inhibition of rolling and L-selectin shedding by neutrophils and eosinophils suggesting that there was no defect in L-selectin shedding in the eosinophil donors who did not respond to GM-CSF. Overall, these studies demonstrate that GM-CSF consistently inhibits interaction of neutrophils with endothelium in vivo, whereas its effect on eosinophil-endothelial interactions is variable. GM-CSF may thus be one factor accounting for the varying percentage of eosinophils and neutrophils recruited to sites of allergic inflammation in different individuals.